Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
-
Lei Lei
,
Ping Zhan
Abstract
Hepatoid adenocarcinoma of the lung (HAL) is a rare malignant tumor that is defined as a primary alpha-fetoprotein (AFP)-producing lung carcinoma. We aimed to identify prognostic factors associated with the survival of patients with HAL using data from the Surveillance, Epidemiology, and End Results (SEER) database. We collected data from patients diagnosed with HAL, adenocarcinoma (ADC), and squamous cell carcinoma (SCC) of the lung between 1975 and 2016 from the SEER database. The clinical features of patients with ADC and SCC of the lung were also analyzed. The clinical features of HALs were compared to ADCs and SCCs. A chi-square test was used to calculate the correlations between categorical variables, and a t test or Mann–Whitney U test was used for continuous variables. The Kaplan–Meier method and Cox regression analysis were used to identify the prognostic factors for the overall survival (OS) of HALs. Two-tailed p values < 0.05 were considered statistically significant. Sixty-five patients with HAL, 2,84,379 patients with ADC, and 1,86,494 with SCC were identified from the SEER database. Fewer males, advanced stages, and more chemotherapy-treated HALs were found. Compared to patients with SCC, patients with HAL were less likely to be male, more likely to be in an advanced stage, and more likely to receive chemotherapy (p < 0.05). The American Joint Committee on Cancer staging was the only prognostic factor for OS in patients with HAL, and stage IV was significantly different from other stages (hazard ratio = 0.045, 95% confidence interval: 0.005–0.398, p = 0.005). Males with HAL were more likely to receive radiotherapy compared to females with HAL (61.8 vs 31.5%, p = 0.034). Younger patients with HAL were more likely to receive chemotherapy (59.4 + 10.2 years vs 69 + 11.3 years, p = 0.001). The primary tumor size of HAL was associated with the location of the primary lesion (p = 0.012). No conventional antitumor therapies, including surgery, chemotherapy, and radiotherapy, were shown to have a significant survival benefit in patients with HAL (p > 0.05). This study showed that stage IV was the only prognostic factor for OS in HALs compared to other clinicopathologic factors. Conventional antitumor therapies failed to show survival benefit; thus, a more effective method by which to treat HAL is needed. Interestingly, the clinical features and the location of the primary lesion were shown to be associated with primary tumor size and treatment in patients with HAL, which have not been reported before.
1 Introduction
Hepatoid adenocarcinoma (ADC) is a rare but malignant tumor that commonly occurs in the stomach [1,2] and also been reported to originate from the pancreas [3], bladder [4], and ovary [5]. The liver-like ADC originating from the lung is referred to as hepatoid adenocarcinoma of the lung (HAL), which has a low incidence (2.3%) among all hepatoid ADCs and a poor prognosis [6]. The median overall survival (OS) of patients with HAL is only 5 months and the 1- and 3-year survival rates are 35 and 14%, respectively [7]. Given the small number of case series and short follow-up interval after surgery, the inconsistent description of characteristics and prognosis of patients with HAL are inevitable.
HAL generally has no specific clinical symptoms and metastatic site predilection, but computed tomography (CT) images may support the diagnosis [8]. The final diagnosis should be confirmed by histologic and immunohistochemical (IHC) methods, which can discriminate HAL from hepatocellular carcinoma [9]. Compared with common types of lung cancer, the poor prognosis of HAL has been reported in several studies [10,11,12]. The prognostic biomarker for HAL remains to be established although an elevated serum α-fetoprotein (AFP) level and positive AFP expression on IHC analysis have been reported as poor prognostic markers [13]. Moreover, there is no standard treatment for HAL. In general, localized HAL surgical be resected, and platinum-based chemotherapy and/or radiation treatment is recommended for patients with advanced or metastatic disease [14]. Nevertheless, the OS is still extremely poor in most patients in late clinical stage HAL [9].
Previous studies have mainly focused on the description of clinical features and the outcome of patients with HAL in case series. Recently, Ayub et al. [7] described a patient with HAL who had an aggressive course of disease and reviewed 41 cases from the SEER database from 1988 to 2014. A large database analysis is still lacking due to the extremely low incidence of this type of lung cancer.
In this study, we reviewed 65 cases of HAL in the same database from 1975 to 2016 and compared the clinicopathologic characteristics of ADC and squamous cell carcinoma (SCC) of the lung to expand the knowledge base pertaining to the clinical features, treatment, and OS-related factors in patients with HAL.
2 Material and methods
2.1 Patient cohort
The Surveillance, Epidemiology, and End Results (SEER) is a free public cancer database. SEER collects data from 18 geographic registries, representing approximately 30% of the US population. We applied for an account to access data and to determine frequency rates. The inclusion criteria for this study included patients with a diagnosis of hepatoid ADC between 1975 and 2016, and a histologic type (code 8576) according to the third edition of the International Classification of Diseases for Oncology (ICD-O-3). The primary site was selected as C34, and the location of the tumor was limited to the lung. There were 65 patients with HAC, 2,84,379 patients with ADC, and 1,86,494 patients with SCC identified from the SEER database.
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Ethical approval and consent to participate: The clinical data used were from the SEER database, which is a public research resource; patient consent and ethical approval for the study were not required.
2.2 Statistical analysis
The incidence and clinical trends for HAC were analyzed using SEER*Stat version 8.3.6 (National Cancer Institute, Bethesda, MD, USA). The incidence was age adjusted to the 2000 US standard population. Annual percentage changes were calculated using the weighted least square method. The clinical factors were analyzed using descriptive statistics, and the chi-square test was used to calculate correlations between categorical variables. Kaplan–Meier curves were generated to assess disease-specific survival, and the differences between groups were compared using log-rank analysis. Cox proportional hazard regression was performed on demographic, clinical, and treatment factors to estimate the survival differences. Cox regression analysis was used for factors that had statistical significance based on univariate analysis. We processed and analyzed the data using statistical software R (version 3.34; http://www.r-project.org). A p < 0.05 indicated statistical significance.
3 Results
3.1 Clinicopathologic characteristics
A total of 65 HALs were identified from the database, including 31 male and 34 female patients. The median age at the time of HAL diagnosis was 64.11 ± 11.704 years, which is similar to the median age at the time of ADC and SCC diagnoses during the same period. There were fewer male patients with HAL than with SCC (47.7 vs 64.8%, p < 0.05). The advanced stages (T3-4 and M1) were more prevalent in HALs than in SCCs (both ps < 0.05). In addition, patients with HAL were more likely to receive chemotherapy than patients with SCC (50.8 vs 31.8%, p < 0.001). Race (white vs not white), lymph node metastases, undergoing surgery, and receiving radiotherapy were not significantly different between patients with HAL and patients with both ADC and SCC (Table 1).
Comparison between HAC, ADC, and SCC
| Variables | HAC (n = 65) | ADC (n = 2,84,379) | SCC (n = 1,86,494) | |
|---|---|---|---|---|
| Age | 64.11 ± 11.704 | 66.39 ± 11.47 | 68.93 ± 9.88 | |
| Sex (%) | Male | 31 (47.7) | 91,755 (48.7) | 68,381 (64.8) |
| Female | 34 (52.3) | 96,830 (51.3) | 37,220 (35.2) | |
| Race (%) | White | 55 (84.6) | 1,52,422 (80.8) | 87,126 (82.5) |
| Not white | 10 (15.4) | 36,163 (19.2) | 18,475 (17.5) | |
| T stage (%) | NA | 36 (55.3) | 2,10,280 (43.9) | 1,46,471 (78.5) |
| T0 | 1 (1.5) | 629 (0.22) | 126 (0.1) | |
| T1 | 3 (4.6) | 17,720 (6.2) | 7,017 (3.8) | |
| T2 | 5 (7.7) | 19,942 (7.0) | 13,406 (7.2) | |
| T3 | 10 (15.4) | 15,583 (5.5) | 9,716 (5.2) | |
| T4 | 10 (15.4) | 17,705 (6.2) | 9,758 (5.2) | |
| N stage (%) | NA | 31 (47.7) | 2,05,668 (72.3) | 1,45,153 (77.8) |
| N negative | 16 (24.6) | 31,396 (11.0) | 17,710 (9.5) | |
| N positive | 18 (27.7) | 47,315 (16.6) | 23,631 (12.7) | |
| M stage (%) | NA | 29 (44.6) | 2,00,134 (70.4) | 1,43,039 (76.7) |
| M0 | 12 (18.5) | 35,650 (12.5) | 27,957 (15.0) | |
| M1 | 24 (36.9) | 48,595 (17.1) | 15,498 (8.3) | |
| Surgery (%) | NA | 56 (86.2) | 5,217 (1.8) | 1,28,918 (69.1) |
| No | 1 (1.5) | 2,01,535 (70.9) | 5,429 (2.9) | |
| Yes | 8 (12.3) | 77,627 (27.3) | 52,147 (27.9) | |
| Radiation (%) | No/unknown | 32 (49.2) | 1,14,066 (40.1) | 91,998 (49.3) |
| Yes | 33 (50.8) | 1,70,313 (59.9) | 94,496 (50.7) | |
| Chemotherapy (%) | No/unknown | 32 (49.2) | 1,71,733 (60.3) | 1,28,330 (68.8) |
| Yes | 33 (50.8) | 1,12,646 (39.6) | 58,164 (31.8) | |
3.2 Survival analysis in patients with HAL
The median OS of the 65 patients with HAL was 5 months (95% confidence interval [CI], 2.55–7.45); the 3- and 5-year survival rates were 7.7 and 6.2%, respectively. A total of 50 patients died during the follow-up period, of which 48 were cancer-specific and 2 were due to other causes (chronic obstructive pulmonary and heart diseases). Multivariant analysis of prognostic factors for OS prediction in patients with HAL included age (hazard ratio [HR], 1.03; 95% CI, 1.01–1.04), chemotherapy (HR, 0.51; 95% CI, 0.36–0.73), and surgery (HR, 0.53; 95% CI, 0.36–0.77), all of which were associated with cancer-specific survival. The American Joint Committee on Cancer (AJCC) staging was the only prognostic factor for OS in patients with HAL; stage IV HAL was significantly different from other stages (HR, 0.045; 95% CI, 0.005–0.398, p = 0.005; Table 2). No conventional antitumor therapies, including surgery, chemotherapy, and radiotherapy, were shown to have a significant survival benefit in patients with HAL (p > 0.05; Figures 1–3).
AJCC stage is the only hazard factor in the Cox proportional hazards model
| AJCC stage | B | HR | 95% CI | p |
|---|---|---|---|---|
| NA | — | — | — | — |
| IA | −2.617 | 0.073 | 0.004–1.233 | 0.070 |
| IB | −24.503 | 0.000 | 0.000–1.500 × 10170 | 0.908 |
| IIB | −14.485 | 0.000 | 0.000–2.897 × 10259 | 0.963 |
| IIIA | −13.218 | 0.000 | 0.000–8.243 × 10119 | 0.929 |
| IIIB | −24.157 | 0.000 | 0.000–2.125 × 10170 | 0.909 |
| IV | −3.091 | 0.045 | 0.005–0.398 | 0.005 |
Surgery does not impact survival of patients with hepatoid adenocarcinoma of the lung.
Chemotherapy does not impact survival of patients with hepatoid adenocarcinoma of the lung.
Radiotherapy does not impact survival of patients with hepatoid adenocarcinoma of the lung.
3.3 Correlation analysis of clinical features in patients with HAL
Male patients with HAL were more likely to receive radiotherapy compared with female patients with HAL (61.8 vs 31.5%, p = 0.034). Patients with HAL treated by chemotherapy were more likely to be younger (59.4 + 10.2 years vs 69 + 11.3 years, p = 0.001). Of the 51 patients with HAL, 30 (58.8%) had primary tumors located in the upper lobes of the lungs, with a median tumor diameter of 173.2 ± 306.2 mm. Ten (19.6%) of 51 HALs with the largest median tumor diameter (626.6 ± 481.9 mm) were located in the lungs with no specific anatomic location. Of 51 HALs, 9 (17.6%) were in the lower lobes of the lungs, with a median tumor diameter of 151.8 ± 318.7 mm. One patient had a tumor in the main bronchus (60 mm in diameter) and a patient had a tumor in the middle lobe (46 mm in diameter). HAL size was associated with the location of the primary lesion (p = 0.012).
4 Discussion
In this study, we analyzed 65 patients with HAL from the SEER database between 1975 and 2016 and found that the clinical stage was the only OS-related factor. Surgery, chemotherapy, and radiotherapy had no significant survival benefit in patients with HAL. Compared with the common types of lung cancer, HALs tended to have closer clinicopathologic characteristics to ADCs than SCCs. Of note, we also identified interactions between gender and radiotherapy, age at diagnosis and chemotherapy, and the primary site and tumor size.
Clinically, HALs are considered to be male dominant with an abnormal AFP level in the serum or expressed on tumor tissue [10,15]. Male patients with HAL have been reported to be ninefold more frequent than female patients with HAL [8]; however, the percentages of males and females with HAL in our study (47.7 vs 52.3%) were closer to the results from a recent study [7]. Furthermore, the prevalence of male patients with SCC was significantly higher than male patients with HAL (64.8 vs 47.7%; p < 0.05). An abnormal AFP level has been associated with poor outcome in patients with HAL and other hepatoid ADCs [10,14,16]; however, the AFP elevation in serum and higher AFP expression in tumor tissues are not necessary criteria for HAL diagnosis [15].
Of note, we further explored the association among those clinical features of HALs which have not been previously reported. We showed that greater than one half (30/51) of primary HALs was located in the upper lobes of the lungs, which is consistent with previous data [7,15,17,18]. The mean size of the primary tumor has been reported to be approximately 7 cm (range, 1–20 cm) [11,18]. At the time of initial diagnosis, lymph node involvement is more common in male patients with HAL than female patients with HAL [8]. In this study, we also found that the number of male patients who received radiotherapy was twice that of female patients. Currently, mediastinal tissue sampling before surgical resection of a HAL is not recommended [7].
In this study, the clinical stage was the only prognostic factor for OS in patients with HAL. Although promising prognostic indicators for HALs are still lacking, the clinical stage is the most likely OS-related factor based on several studies. Patients with stages I–II HAL could have a disease-free survival of up to 7 years after surgery and adjuvant therapy [19,20,21]. These findings also suggest that curative resection and reasonable adjuvant chemotherapy and/or radiotherapy may influence the outcome of HALs; however, our findings did not show a statistically significant OS benefit from any of the abovementioned therapies. A better understanding of the biology of this rare but aggressive disease could facilitate the identification of effective therapeutic targets and drugs in the future.
Currently no standard guidelines are available for the treatment of HALs; however, surgical resection for patients in an early stage and palliative chemotherapy with platinum and radiotherapy for patients in a late stage are recommended. Although we did not present an analysis of specific chemotherapies for HALs due to a lack of such data in the SEER database, the lack of OS benefit by all of the conventional therapies in our study is noteworthy. Fortunately, encouraging data by new therapies have recently been reported. Specifically, a patient with HAL stage IV had a good response and tolerated targeted therapy with sorafenib and platinum-based chemotherapy; the median OS was 11 months [22]. A patient with an HAL stage IV has been reported to respond surprisingly well to anti-PD-L1 durvalumab therapy, despite all negative test results for EGFR, KRAS, ALK, ROS1, and PD-L1 [23].
Several limitations of this study should be mentioned. First, it was a retrospective public database analysis and bias of case selection could not be excluded. As far as we know, however, this is the first study of HALs by way of comparison to a large number of common NSCLC types. Second, information about potential prognostic factors, including the serum AFP level, smoking status, CT findings, and genetic mutations, are not included in the SEER database. In our analysis, we included all available clinicopathologic factors for HALs from the SEER database. Finally, due to the limited number of HALs, the comparison results of HALs with ADCs and SCCs should not be applied in practice due to the potential statistical bias. Furthermore, we did not perform a subgroup analysis of treatments by different stages for survival benefit. A corollary study with a larger sample size of patients with HAL should be conducted to verify our conclusions.
5 Conclusion
In summary, we found that HALs are an aggressive and highly heterogeneous type of lung cancer, thus earlier diagnosis and better treatment are needed. HAL stage IV was the only negative prognostic factor for OS compared with other clinical stages. Interestingly, gender, age at the time of diagnosis, and location of the primary lesion could influence treatment and tumor size of HALs, which have not been previously reported.
Acknowledgments
This study was supported in part by grants from the Medical Scientific Research Foundation of Zhejiang Province of China (2019RC027), the Zhejiang Traditional Chinese Medicine Science Fund Project (2020ZB037), Zhejiang Tranditional Chinese Medicine Science Fund Project (2020ZQ013), Scientific Research Foundation of Zhejiang Medical Association (2019ZYC-A76), Huilan Public-Hanson Pharmaceutical Lung Cancer Precision Medical Research Special Fund Project Foundation (HL-HS2020-5), and the Xisike-Hanson Cancer Research Foundation (Y-HS2019-20).
-
Conflict of interest: There are no conflicts of interest to declare.
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© 2021 Lei Lei et al., published by De Gruyter
This work is licensed under the Creative Commons Attribution 4.0 International License.
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- A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
- Clinical and prognostic features of MMP-2 and VEGF in AEG patients
- The value of miR-510 in the prognosis and development of colon cancer
- Functional implications of PABPC1 in the development of ovarian cancer
- Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
- Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
- Prediction of improvement after anterior cruciate ligament reconstruction
- Effluent Osteopontin levels reflect the peritoneal solute transport rate
- circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
- Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
- Association between hair cortisol concentration and metabolic syndrome
- Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
- Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
- Knee alterations in rheumatoid arthritis: Comparison of US and MRI
- Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
- lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
- Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
- Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
- Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
- Travelers’ vaccines and their adverse events in Nara, Japan
- Association between Tfh and PGA in children with Henoch–Schönlein purpura
- Can exchange transfusion be replaced by double-LED phototherapy?
- circ_0005962 functions as an oncogene to aggravate NSCLC progression
- Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
- Serum intact fibroblast growth factor 23 in healthy paediatric population
- Algorithm of rational approach to reconstruction in Fournier’s disease
- A meta-analysis of exosome in the treatment of spinal cord injury
- Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
- Dexmedetomidine may decrease the bupivacaine toxicity to heart
- Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
- Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
- External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
- miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
- HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
- Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
- Cell population data in identifying active tuberculosis and community-acquired pneumonia
- Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
- Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
- 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
- Association of gene polymorphisms with women urinary incontinence
- Influence of COVID-19 pandemic on stress levels of urologic patients
- miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
- miR-519d downregulates LEP expression to inhibit preeclampsia development
- Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
- Fluorescent light energy modulates healing in skin grafted mouse model
- Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
- Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
- Severe postoperative hyperbilirubinemia in congenital heart disease
- Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
- Clinical factors predicting ureteral stent failure in patients with external ureteral compression
- Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
- Triple-Endobutton and clavicular hook: A propensity score matching analysis
- Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
- Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
- miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
- Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
- The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
- Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
- No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
- circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
- Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
- Educational program for orthopedic surgeons’ influences for osteoporosis
- Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
- GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
- lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
- Anticoagulation is the answer in treating noncritical COVID-19 patients
- Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
- Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
- VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
- Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
- Treatment of osteoporosis with teriparatide: The Slovenian experience
- New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
- Superenhancer–transcription factor regulatory network in malignant tumors
- β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
- Clinical features of atypical tuberculosis mimicking bacterial pneumonia
- Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
- Effect of electromagnetic field on abortion: A systematic review and meta-analysis
- miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
- MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
- Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
- miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
- Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
- MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
- Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
- circATP2A2 promotes osteosarcoma progression by upregulating MYH9
- Prognostic role of oxytocin receptor in colon adenocarcinoma
- Review Articles
- The function of non-coding RNAs in idiopathic pulmonary fibrosis
- Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
- Role of cesarean section in the development of neonatal gut microbiota: A systematic review
- Small cell lung cancer transformation during antitumor therapies: A systematic review
- Research progress of gut microbiota and frailty syndrome
- Recommendations for outpatient activity in COVID-19 pandemic
- Rapid Communication
- Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
- Use of microspheres in embolization for unruptured renal angiomyolipomas
- COVID-19 cases with delayed absorption of lung lesion
- A triple combination of treatments on moderate COVID-19
- Social networks and eating disorders during the Covid-19 pandemic
- Letter
- COVID-19, WHO guidelines, pedagogy, and respite
- Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
- COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
- What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
- Case Report
- Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
- CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
- Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
- Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
- Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
- Pulmonary parenchymal involvement caused by Tropheryma whipplei
- Mediastinal mixed germ cell tumor: A case report and literature review
- Ovarian female adnexal tumor of probable Wolffian origin – Case report
- Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
- Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
- Primary orbital ganglioneuroblastoma: A case report
- Primary aortic intimal sarcoma masquerading as intramural hematoma
- Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
- Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
- Chondroblastoma of mandibular condyle: Case report and literature review
- Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
- Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
- Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
- High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
- Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
- Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
- Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
- Retraction
- Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
- An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
- Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
Articles in the same Issue
- Research Articles
- Identification of ZG16B as a prognostic biomarker in breast cancer
- Behçet’s disease with latent Mycobacterium tuberculosis infection
- Erratum
- Erratum to “Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome”
- Research Articles
- GPR37 promotes the malignancy of lung adenocarcinoma via TGF-β/Smad pathway
- Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
- Additional baricitinib loading dose improves clinical outcome in COVID-19
- The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
- SLC12A8 plays a key role in bladder cancer progression and EMT
- LncRNA ATXN8OS enhances tamoxifen resistance in breast cancer
- Case Report
- Serratia marcescens as a cause of unfavorable outcome in the twin pregnancy
- Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background
- Research Articles
- TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
- CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
- LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
- Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
- Rapid Communication
- COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
- Case Report
- Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
- An infertile female delivered a baby after removal of primary renal carcinoid tumor
- Research Articles
- Hypertension, BMI, and cardiovascular and cerebrovascular diseases
- Case Report
- Coexistence of bilateral macular edema and pale optic disc in the patient with Cohen syndrome
- Research Articles
- Correlation between kinematic sagittal parameters of the cervical lordosis or head posture and disc degeneration in patients with posterior neck pain
- Review Articles
- Hepatoid adenocarcinoma of the lung: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database
- Research Articles
- Thermography in the diagnosis of carpal tunnel syndrome
- Pemetrexed-based first-line chemotherapy had particularly prominent objective response rate for advanced NSCLC: A network meta-analysis
- Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
- The influence of smoking in minimally invasive spinal fusion surgery
- Impact of body mass index on left atrial dimension in HOCM patients
- Expression and clinical significance of CMTM1 in hepatocellular carcinoma
- miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
- Comparison of multiple flatfoot indicators in 5–8-year-old children
- Early MRI imaging and follow-up study in cerebral amyloid angiopathy
- Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
- miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
- Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
- Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
- Review Articles
- The ambiguous role of mannose-binding lectin (MBL) in human immunity
- Case Report
- Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
- Fertility problems in males carrying an inversion of chromosome 10
- Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
- Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
- Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
- Skull hemophilia pseudotumor: A case report
- Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
- Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
- Clinicopathologic features of Good’s syndrome: Two cases and literature review
- Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
- Research Articles
- Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
- Significance of nucleic acid positive anal swab in COVID-19 patients
- circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
- Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
- Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
- Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
- Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
- Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
- FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
- Platelet-rich fibrin: Basics of biological actions and protocol modifications
- Accurate diagnosis of prostate cancer using logistic regression
- miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
- Prognostic significance of TRIM28 expression in patients with breast carcinoma
- Integrative bioinformatics analysis of KPNA2 in six major human cancers
- Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
- A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
- Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
- Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
- Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
- COVID-19 severity in relation to sociodemographics and vitamin D use
- Clinical analysis of 11 cases of nocardiosis
- Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
- Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
- Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
- Relation between IL-8 level and obstructive sleep apnea syndrome
- circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
- Nomogram prediction model for renal anaemia in IgA nephropathy patients
- Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
- NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
- A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
- Clinical and prognostic features of MMP-2 and VEGF in AEG patients
- The value of miR-510 in the prognosis and development of colon cancer
- Functional implications of PABPC1 in the development of ovarian cancer
- Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
- Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
- Prediction of improvement after anterior cruciate ligament reconstruction
- Effluent Osteopontin levels reflect the peritoneal solute transport rate
- circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
- Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
- Association between hair cortisol concentration and metabolic syndrome
- Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
- Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
- Knee alterations in rheumatoid arthritis: Comparison of US and MRI
- Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
- lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
- Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
- Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
- Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
- Travelers’ vaccines and their adverse events in Nara, Japan
- Association between Tfh and PGA in children with Henoch–Schönlein purpura
- Can exchange transfusion be replaced by double-LED phototherapy?
- circ_0005962 functions as an oncogene to aggravate NSCLC progression
- Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
- Serum intact fibroblast growth factor 23 in healthy paediatric population
- Algorithm of rational approach to reconstruction in Fournier’s disease
- A meta-analysis of exosome in the treatment of spinal cord injury
- Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
- Dexmedetomidine may decrease the bupivacaine toxicity to heart
- Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
- Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
- External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
- miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
- HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
- Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
- Cell population data in identifying active tuberculosis and community-acquired pneumonia
- Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
- Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
- 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
- Association of gene polymorphisms with women urinary incontinence
- Influence of COVID-19 pandemic on stress levels of urologic patients
- miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
- miR-519d downregulates LEP expression to inhibit preeclampsia development
- Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
- Fluorescent light energy modulates healing in skin grafted mouse model
- Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
- Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
- Severe postoperative hyperbilirubinemia in congenital heart disease
- Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
- Clinical factors predicting ureteral stent failure in patients with external ureteral compression
- Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
- Triple-Endobutton and clavicular hook: A propensity score matching analysis
- Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
- Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
- miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
- Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
- The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
- Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
- No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
- circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
- Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
- Educational program for orthopedic surgeons’ influences for osteoporosis
- Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
- GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
- lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
- Anticoagulation is the answer in treating noncritical COVID-19 patients
- Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
- Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
- VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
- Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
- Treatment of osteoporosis with teriparatide: The Slovenian experience
- New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
- Superenhancer–transcription factor regulatory network in malignant tumors
- β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
- Clinical features of atypical tuberculosis mimicking bacterial pneumonia
- Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
- Effect of electromagnetic field on abortion: A systematic review and meta-analysis
- miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
- MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
- Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
- miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
- Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
- MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
- Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
- circATP2A2 promotes osteosarcoma progression by upregulating MYH9
- Prognostic role of oxytocin receptor in colon adenocarcinoma
- Review Articles
- The function of non-coding RNAs in idiopathic pulmonary fibrosis
- Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
- Role of cesarean section in the development of neonatal gut microbiota: A systematic review
- Small cell lung cancer transformation during antitumor therapies: A systematic review
- Research progress of gut microbiota and frailty syndrome
- Recommendations for outpatient activity in COVID-19 pandemic
- Rapid Communication
- Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
- Use of microspheres in embolization for unruptured renal angiomyolipomas
- COVID-19 cases with delayed absorption of lung lesion
- A triple combination of treatments on moderate COVID-19
- Social networks and eating disorders during the Covid-19 pandemic
- Letter
- COVID-19, WHO guidelines, pedagogy, and respite
- Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
- COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
- What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
- Case Report
- Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
- CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
- Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
- Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
- Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
- Pulmonary parenchymal involvement caused by Tropheryma whipplei
- Mediastinal mixed germ cell tumor: A case report and literature review
- Ovarian female adnexal tumor of probable Wolffian origin – Case report
- Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
- Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
- Primary orbital ganglioneuroblastoma: A case report
- Primary aortic intimal sarcoma masquerading as intramural hematoma
- Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
- Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
- Chondroblastoma of mandibular condyle: Case report and literature review
- Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
- Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
- Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
- High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
- Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
- Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
- Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
- Retraction
- Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
- An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
- Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
