Startseite Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma
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Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma

  • Yong-Xin Cui und Xian-Shuang Su EMAIL logo
Veröffentlicht/Copyright: 17. April 2020
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Open Medicine
Aus der Zeitschrift Open Medicine Band 15 Heft 1

Abstract

Objective

Programmed cell death-ligand 1 (PD-L1) expression has been shown to play important roles in various types of cancer. However, the role of PD-L1 expression has not been conclusively reported in patients with oral squamous cell carcinoma (OSCC). Accordingly, in this meta-analysis, we investigated the clinicopathological value of PD-L1 expression in patients with OSCC.

Methods

Google Scholar, PubMed, EMBASE, and CNKI databases were searched to find relevant studies published through to September 16, 2019. The relationships between PD-L1 expression in patients with OSCC and clinicopathological features were assessed using risk ratio (RR) and 95% confidence intervals (CIs).

Results

Sixteen studies including 1989 participants were included. The results indicated that high PD-L1 expression was correlated with sex (RR = 1.28, 95% CI: 1.16–1.42, P < 0.001), N stage (RR = 1.19, 95% CI: 1.06–1.33, P = 0.003), M stage (RR = 1.64, 95% CI: 1.01–2.66, P = 0.044), low differentiation (RR = 1.16, 95% CI: 1.01–1.33, P = 0.034), and human papilloma virus infection (RR = 1.38, 95% CI: 1.14–1.68, P = 0.001), but unrelated to TNM stage or T stage. There was no significant publication bias in the studies included in this analysis.

Conclusions

This meta-analysis revealed that high PD-L1 expression in patients with OSCC was correlated with clinicopathological features. Further large-scale studies are necessary to confirm our results.

Keywords: Oral squamous cell carcinom; Programmed cell death-ligand 1; Clinicopathological features; Meta-analysis

1 Introduction

Oral cancer is a major public health concern worldwide; approximately 350,000 patients are newly diagnosed with oral cancer each year, and oral cancer causes approximately 170,000 deaths annually [1]. Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of malignant oral carcinomas, and the 5-year survival rate is only approximately 50% [2, 3]. Owing to the high rate of metastasis in patients with OSCC, the prognosis tends to be poor [4]. Prediction of prognosis plays a critical role in the treatment of OSCC and is usually based on the tumor-node-metastasis (TNM) classification system; lymph node metastases and the presence of distant metastases are associated with a poor prognosis [5, 6]. Despite recent advancements in various therapies, including radiotherapy, chemotherapy, and surgery, the survival rates of patients with OSCC have not improved [2]. Thus, the identification of novel prognostic markers is urgently needed to improve personalized treatment approaches and clinical outcomes in patients with OSCC.

Programmed cell death-ligand 1 (PD-L1), also known as B7-H1 or CD274, is a member of the costimulatory factor superfamily [7]. PD-L1 is expressed in various types of tumor cells and in immune cells, including activated B cells and T cells, macrophages, and dendritic cells [8]. When the programmed cell death-1 (PD-1)/PD-L1 axis is highly expressed in a healthy immune system, activation of this pathway restricts autoimmunity and limits T-cell activity in an inflammatory response to infection [9]. In contrast, overexpression of PD-L1 in carcinoma cells blocks the activation of T cells, exhausts T cells, and triggers apoptosis in effector T cells, thereby impairing cytokine production and promoting tumor growth [10, 11, 12].

Previous studies have reported the prognostic value of PD-L1 expression in many types of malignant solid tumors, such as pancreatic carcinoma [13], non-small cell lung carcinoma [14], prostate cancer [15], gastric carcinoma [16], and breast cancer [17]. Moreover, although several studies have investigated the associations between PD-L1 expression and clinicopathological characteristics in patients with OSCC, the results remain contradictory [18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32]. For example, Straub and colleagues found that PD-L1 overexpression is closely related to lymph node metastasis and is correlated with poor overall survival in patients with OSCC [24]. In contrast, Hong et al. revealed that high PD-L1 expression is associated with better prognosis in patients with OSCC [19]. In a study by Cho and colleagues, however, PD-L1 expression does not affect survival rates in patients with OSCC [32].

In this study, in order to clarify the role of PD-L1 in OSCC, we performed a meta-analysis of PD-L1 expression and clinicopathological features in patients with OSCC.

2 Methods

2.1 Literature search

A systematic literature search was performed of PubMed, EMBASE, Google Scholar, and CNKI up to September 16, 2019 using the following search terms: (“mouth” OR “oral”) AND (“carcinoma” OR “tumor” OR “neoplasm” OR “cancer”) AND (“B7-H1” OR “programmed cell death ligand 1” OR “PD-L1”). The study was performed according to the Statement of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [33].

2.2 Inclusion and exclusion criteria

The included studies met the following inclusion criterion: (a) participants were histologically diagnosed with OSCC; (b) articles were written in English or Chinese with full text available, and humans were used as the study subjects; (c) the expression level of the PD-L1 gene was estimated in OSCC tissues; (d) the relationship of PD-L1 expression with clinicopathological features was investigated in OSCC patients; (e) studies had sufficient materials to estimate relative risk (RR) with corresponding 95% confidence intervals (95% CIs). Exclusion criteria were as follows: (a) reviews, editorials, conference abstracts, and case reports; and (b) studies that had insufficient data.

2.3 Data extraction and quality assessment

The available data for the included studies were independently extracted by two authors. The following data were extracted: first author, country, ethnicity, publication year, detection method, and clinicopathological parameters. Disagreement was settled through discussion between authors. The Newcastle-Ottawa-Scale (NOS) was applied to estimate the quality of the included studies [34].

2.4 Statistical analysis

The relationships between PD-L1 expression in patients with OSCC and clinicopathological characteristics were assessed using RR and 95% CIs. Cochrane’s Q tests and the I2 statistic were carried out to evaluate between-study heterogeneity. Significant heterogeneity was defined as P < 0.1 or I2 > 50%, and RR were then pooled using the random-effect model [35]; Or else, a fixed-effect model was chosen [36]. Additionally, we performed a sensitivity analysis to determine the stability of the pooled values. To estimate potential publication bias, Egger linear regression tests and Begg’s funnel plots were used [37, 38]. All analyses were performed using Stata 15.0 software (Stata Corp., College Station, TX, USA).

3 Results

3.1 Literature search results

Figure 1 shows the literature search process. In total, 117 studies were selected from our database search. Duplicates were deleted, 83 articles were screened, and 54 records were further removed. The full text of the remaining 29 articles was read. Finally, 15 articles were included in the current analysis [18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32].

Figure 1 Flow chart of study identification.
Figure 1

Flow chart of study identification.

3.2 Description of the included studies

Sixteen retrospective studies including 1989 participants were included in our meta-analysis of the association between PD-L1 expression and clinicopathological features in patients with OSCC. Among the 15 articles, data describing sex (1947 patients; female versus male), T stage (1768 patients; T3/T4 versus T1/T2), N stage (1663 patients; N1–N3 versus N0), M stage (581 patients; M1 versus M0), TNM stage (1351 patients; III/IV versus I/II), histological grade (1486 patients; poorly/moderately versus well differentiated), recurrence status (333 patients; yes versus no), and human papilloma virus (HPV) status (935 patients; positive versus negative) were included. Among the 16 studies, eight studies evaluated Asians, and eight studies evaluated Caucasians. The total sample size was 1989, ranging from 24 to 305. The included articles were published between 2011 and 2019. The expression level of PD-L1 in patients with OSCC was detected using immuno-histochemistry. The quality of the included studies was evaluated by the NOS, and the scores for the included literature ranged from 6 to 9, indicating that the enrolled studies were of a relatively high quality. Detailed information for the included studies is presented in Table 1.

Table 1

Characteristics of included studies.

TNMPD-L1 expression
AuthorYearCountryEthnicityTotal (n)stageDetection methodPositiveNegativeNOS
Cho2011KoreaAsian45I-IVIHC26196
Ukpo2013USACaucasian181I-IVIHC84977
Lin2015ChinaAsian305I-IVIHC1331727
Oliveira-Costa2015BrazilCaucasian142I-IIIIHC47498
Hong2016AustraliaCaucasian99I-IVIHC69307
Kim2015KoreaAsian133I-IVIHC90439
Ock(a)2016KoreaAsian50I-IVIHC32188
Ock(b)2016KoreaAsian91I-IVIHC59328
Satgunaseelan2016AustraliaCaucasian217NAIHC401779
Straub2016GermanyCaucasian80I-IVIHC36447
Meulenaere2017BelgiumCaucasian99I-IVIHC22728
Hirai2017JapanAsian24I-IVIHC13117
Kogashiwa2017JapanAsian84I-IVIHC44407
Troeltzsch2016GermanyCaucasian88I-IVIHC26628
Hong2019AustraliaCaucasian214I-IVIHC145699
Sato2019JapanAsian137I-IVIHC81568

  1. PD-L1, programmed cell death ligand 1; NA, not available; IHC, immunohistochemical; NOS, Newcastle-Ottawa-Scale.

3.3 Meta-analysis results

3.3.1 Sex

Fifteen studies (1947 patients; 458 women and 1489 men) were included for evaluation of the relationship between PD-L1 expression and sex in patients with OSCC. There was a low degree of heterogeneity among the studies (I2 = 23.0%, P = 0.199); thus, the fixed-effect model was used for pooled analysis. The results indicated a statistically significant relationship between high PD-L1 expression and female sex (RR = 1.28, 95% CI: 1.16–1.42, P < 0.001). Subgroup analysis by race indicated that high PD-L1 expression was associated significantly with women in both Caucasian and Asian populations (Table 2 and Figure 2).

Figure 2 Forest plot of RRs and 95% CIs for the association between PD-L1 expression and sex. (A) Overall population; (B) stratified by ethnicity.
Figure 2

Forest plot of RRs and 95% CIs for the association between PD-L1 expression and sex. (A) Overall population; (B) stratified by ethnicity.

Table 2

Correlation between clinical variables and PD-L1 expression in OSCC.

HeterogeneityAssociation
Clinical variablesStudiesI2p-valueRR95%CIp-valueEgger’s
Gender14230.1991.281.16-1.42<0.0010.203
          Asian600.5581.391.23-1.58<0.001
          Caucasian830.80.1821.181.01-1.370.039
T stage1413.20.3091.030.94-1.130.5460.879
          Asian600.90.930.80-1.070.295
          Caucasian829.10.1961.120.98-1.270.094
N stage1340.60.0631.191.06-1.330.0030.575
          Asian500.6390.980.82-1.180.845
          Caucasian840.40.1091.341.16-1.56<0.001
M stage368.70.0411.641.01-2.660.0440.12
TNM stage949.60.0370.90.75-1.080.2520.264
          Asian563.50.0180.920.70-1.200.537
          Caucasian419.20.2940.860.68-1.100.235
Differentiation1100.6241.161.01-1.330.0340.942
          Asian400.721.160.94-1.430.168
          Caucasian7130.3311.160.97-1.390.106
Recurrence400.5850.750.57-1.000.0460.291
HPV-Positive759.60.0151.381.14-1.680.0010.953
          Asian200.7131.221.02-1.460.011
          Caucasian570.80.0081.541.10-2.140.027

  1. PD-L1, programmed cell death ligand 1; CI, confidence interval; RR, relative risks.

3.3.2 N stage

Thirteen studies (1663 patients; 958 with N1–N3 stage and 705 with N0 stage) were included for evaluation of the relationship between PD-L1 expression and lymph node metastasis in patients with OSCC. Moderate heterogeneity was found among the studies (I2 = 40.6%, P = 0.063); thus, the fixed-effect model was used for pooled analysis. The results indicated that there was a significant relationship between high PD-L1 expression and lymph node metastasis (N1–N3; RR = 1.19, 95% CI: 1.06–1.33, P = 0.003). Subgroup analysis by race indicated that high PD-L1 expression was significantly correlated with lymph node metastasis among Caucasians (RR = 1.34, 95% CI: 1.16–1.56, P < 0.001; Table 2 and Figure 3).

Figure 3 Forest plot of RRs and 95% CIs for the association between PD-L1 expression and N stage. (A) Overall population; (B) stratified by ethnicity.
Figure 3

Forest plot of RRs and 95% CIs for the association between PD-L1 expression and N stage. (A) Overall population; (B) stratified by ethnicity.

3.3.3 Histological grade

Twelve studies (1486 patients; 1149 with poorly/moderately differentiated disease and 337 with well differentiated disease) were included for assessment of the association between histological grade and PD-L1 expression. No significant heterogeneity was found (I2 = 0%, P = 0.624); thus, the fixed-effect model was used for pooled analysis. The results revealed a significant relationship between high PD-L1 expression and advanced histological grade (poorly/moderately differentiated; RR = 1.16, 95% CI: 1.01– 1.33, P = 0.034). In the stratification according to ethnicity, we found no significant relationship between high PD-L1 expression and different histological grades (Table 2 and Figure 4).

Figure 4 Forest plot of RRs and 95% CIs for the association between PD-L1 expression and histological grade. (A) Overall population; (B) stratified by ethnicity.
Figure 4

Forest plot of RRs and 95% CIs for the association between PD-L1 expression and histological grade. (A) Overall population; (B) stratified by ethnicity.

3.3.4 HPV status

Eight studies (935 patients; 424 with HPV-associated disease and 511 without HPV-associated disease) were included for evaluation of the relationship between HPV status and PD-L1 expression. Moderate heterogeneity was found among the studies (I2 = 59.6%, P = 0.015); thus, a random-effect model was used for pooled analysis. The results demonstrated a significant association between high PD-L1 expression and HPV-associated OSCC (RR = 1.38, 95% CI: 1.14–1.68, P = 0.001). In the subgroup analysis stratified based on ethnicity, we found that high PD-L1 expression was significant correlated with HPV-as-sociated OSCC among Caucasian and Asian populations (Table 2 and Figure 5)

Figure 5 Forest plot of RRs and 95% CIs for the association between PD-L1 expression and HPV status. (A) Overall population; (B) stratified by ethnicity.
Figure 5

Forest plot of RRs and 95% CIs for the association between PD-L1 expression and HPV status. (A) Overall population; (B) stratified by ethnicity.

3.3.5 Other clinicopathological features

Four studies (333 patients; 85 with recurrence and 248 without recurrence) were included for evaluation of the relationship between PD-L1 expression and recurrence status in patients with OSCC. No heterogeneity was found (I2 = 0%, P = 0.585); thus, a fixed-effect model was used for the pooled analysis. The results revealed a significant relationship between high PD-L1 expression and recurrence (RR = 0.75, 95% CI: 0.57–1.00, P = 0.046). However, high expression of PD-L1 was not significantly correlated with T stage (RR = 1.03, 95% CI: 0.94–1.13, P = 0.546) or TNM stage (RR = 0.90, 95% CI: 0.75–1.08, P = 0.252; Table 2).

3.4 Sensitivity analysis and publication bias

We performed a sensitivity analysis by sequentially deleting each study individually; the results indicated that the pooled RR was unaffected, as shown in Figure 6. Potential publication bias was evaluated using Egger’s test and Begg’s funnel. Funnel plots were largely symmetric, indicating no obvious publication bias, as shown in Figure 7 and Table 2.

Figure 6 Sensitivity analysis for the association between PD-L1 expression and (A) sex; (B) grade; (C) N stage; and (D) HPV status.
Figure 6

Sensitivity analysis for the association between PD-L1 expression and (A) sex; (B) grade; (C) N stage; and (D) HPV status.

Figure 7 Begg’s funnel plot for the association between PD-L1 expression and (A) sex and (B) N stage.
Figure 7

Begg’s funnel plot for the association between PD-L1 expression and (A) sex and (B) N stage.

4 Discussion

PD-L1, an immunoinhibitory receptor that was first described in 1992 by Ishida, is expressed in tumor cells and various types of immune cells, including activated B cells and T cells, macrophages, and dendritic cells [8, 39]. PD-L1 is an essential regulatory molecule in the immune system and is critical for the immune escape mechanisms of many types of cancer cells [40]. Overexpression of PD-L1 results in an immunosuppressive tumor microenvironment and prevents T cells from mediating cytolysis in numerous solid tumors. In some tumor cells, PD-L1 blocks the activation of T cells, exhausts T cells, triggers apoptosis in effector T cells, and impairs cytokine production, resulting in tumor growth [10, 11, 12].

PD-L1’s immune checkpoint response has been extensively studied and plays predominant roles in immune surveillance during tumor development and immune escape of cancer cells [41]. Immune checkpoint inhibitors, including nivolumab and pembrolizumab, have been approved to treat OSCC [42, 43, 44, 45, 46]. Despite the importance of the immune checkpoint, the clinicopathological effects of PD-L1 expression in patients with OSCC remain unclear. In this study, we performed a comprehensive and systematic analysis of the clinicopathological significant of PD-L1 expression in patients with OSCC. Our findings showed that high PD-L1 expression was significantly correlated with certain clinicopathological parameters, including female sex, lymph node metastasis (N1–N3), and advanced histological grade (poorly/moderately differentiated), in patients with OSCC.

In a previous study by Lin et al., high PD-L1 expression was found to be associated with low overall survival in patients with OSCC, and PD-L1 was highly expressed in women [30], consistent with our results. However, there was no significant correlation between high PD-L1 expression and sex in patients with OSCC in another study [47]. Thus, it remains unclear whether sex plays a role in influencing PD-L1 expression in patients with OSCC. In our study, the results demonstrated that high PD-L1 expression was significantly related to lymph node metastasis and advanced histological grade, consistent with some previous studies [19, 32]. These characteristics suggest that deviations in the PD-L1 pathway in malignant tumors are associated with more malignant clinical conditions, including tumor prognosis and progression. Moreover, we also investigated the association between HPV status and high PD-L1 expression in patients with OSCC; the results showed that high PD-L1 expression was significantly related to HPV-associated OSCC, consistent with previous studies [19]. However, no significant relationship was found between the high PD-L1 expression and HPV status in a different study [31], potentially because of the limited sample size. Overall, our meta-analysis revealed that high PD-L1 expression was associated with several clinicopathological features in patients with OSCC, suggesting that PD-L1 may play a role in the clinical diagnosis and prognosis of OSCC.

There were several limitations to our current results. First, although 16 studies were selected, the sample size was relatively small, with only 1989 patients included in the evaluated studies. Second, the studies were published in Chinese and English, which may have resulted in publication bias; however, we detected no publication bias in this study. Third, significant heterogeneity was observed between studies; thus, we implemented this meta-analysis using random-effect models and sensitivity analysis to verify the reliability of our results.

5 Conclusions

Our current meta-analysis indicated that high PD-L1 expression in patients with OSCC was correlated with clinicopathological features, suggesting the potential roles of PD-L1 in the diagnosis and prognosis of patients with OSCC. To verify our results, further large-scale studies are needed.

Acknowledgements

None.

  1. Ethical approval: Not applicable.

  2. Funding: None.

  3. Declaration of competing interests: None.

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Received: 2019-10-31
Accepted: 2020-01-17
Published Online: 2020-04-17

© 2020 Yong-Xin Cui, Xian-Shuang Su, published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

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https://doi.org/10.1515/med-2020-0041
Schlagwörter für diesen Artikel
Oral squamous cell carcinom; Programmed cell death-ligand 1; Clinicopathological features; Meta-analysis
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Research Article
  2. MicroRNA-451b participates in coronary heart disease by targeting VEGFA
  3. Case Report
  4. A combination therapy for Kawasaki disease with severe complications: a case report
  5. Vitamin E for prevention of biofilm-caused Healthcare-associated infections
  6. Research Article
  7. Differential diagnosis: retroperitoneal fibrosis and oncological diseases
  8. Optimization of the Convolutional Neural Networks for Automatic Detection of Skin Cancer
  9. NEAT1 promotes LPS-induced inflammatory injury in macrophages by regulating miR-17-5p/TLR4
  10. Plasma matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 as prognostic biomarkers in critically ill patients
  11. Effects of extracorporeal magnetic stimulation in fecal incontinence
  12. Case Report
  13. Mixed germ cell tumor of the endometrium: a case report and literature review
  14. Bowel perforation after ventriculoperitoneal-shunt placement: case report and review of the literature
  15. Research Article
  16. Prognostic value of lncRNA HOTAIR in colorectal cancer : a meta-analysis
  17. Case Report
  18. Treatment of insulinomas by laparoscopic radiofrequency ablation: case reports and literature review
  19. Research Article
  20. The characteristics and nomogram for primary lung papillary adenocarcinoma
  21. Undiagnosed pheochromocytoma presenting as a pancreatic tumor: A case report
  22. Bioinformatics Analysis of the Expression of ATP binding cassette subfamily C member 3 (ABCC3) in Human Glioma
  23. Diagnostic value of recombinant heparin-binding hemagglutinin adhesin protein in spinal tuberculosis
  24. Primary cutaneous DLBCL non-GCB type: challenges of a rare case
  25. LINC00152 knock-down suppresses esophageal cancer by EGFR signaling pathway
  26. Case Report
  27. Life-threatening anaemia in patient with hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)
  28. Research Article
  29. QTc interval predicts disturbed circadian blood pressure variation
  30. Shoulder ultrasound in the diagnosis of the suprascapular neuropathy in athletes
  31. The number of negative lymph nodes is positively associated with survival in esophageal squamous cell carcinoma patients in China
  32. Differentiation of pontine infarction by size
  33. RAF1 expression is correlated with HAF, a parameter of liver computed tomographic perfusion, and may predict the early therapeutic response to sorafenib in advanced hepatocellular carcinoma patients
  34. LncRNA ZEB1-AS1 regulates colorectal cancer cells by miR-205/YAP1 axis
  35. Tissue coagulation in laser hemorrhoidoplasty – an experimental study
  36. Classification of pathological types of lung cancer from CT images by deep residual neural networks with transfer learning strategy
  37. Enhanced Recovery after Surgery for Lung Cancer Patients
  38. Case Report
  39. Streptococcus pneumoniae-associated thrombotic microangiopathy in an immunosuppressed adult
  40. Research Article
  41. The characterization of Enterococcus genus: resistance mechanisms and inflammatory bowel disease
  42. Case Report
  43. Inflammatory fibroid polyp: an unusual cause of abdominal pain in the upper gastrointestinal tract A case report
  44. Research Article
  45. microRNA-204-5p participates in atherosclerosis via targeting MMP-9
  46. LncRNA LINC00152 promotes laryngeal cancer progression by sponging miR-613
  47. Can keratin scaffolds be used for creating three-dimensional cell cultures?
  48. miRNA-186 improves sepsis induced renal injury via PTEN/PI3K/AKT/P53 pathway
  49. Case Report
  50. Delayed bowel perforation after routine distal loopogram prior to ileostomy closure
  51. Research Article
  52. Diagnostic accuracy of MALDI-TOF mass spectrometry for the direct identification of clinical pathogens from urine
  53. The R219K polymorphism of the ATP binding cassette subfamily A member 1 gene and susceptibility to ischemic stroke in Chinese population
  54. miR-92 regulates the proliferation, migration, invasion and apoptosis of glioma cells by targeting neogenin
  55. Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma
  56. NF2 inhibits proliferation and cancer stemness in breast cancer
  57. Body composition indices and cardiovascular risk in type 2 diabetes. CV biomarkers are not related to body composition
  58. S100A6 promotes proliferation and migration of HepG2 cells via increased ubiquitin-dependent degradation of p53
  59. Review Article
  60. Focus on localized laryngeal amyloidosis: management of five cases
  61. Research Article
  62. NEAT1 aggravates sepsis-induced acute kidney injury by sponging miR-22-3p
  63. Pericentric inversion in chromosome 1 and male infertility
  64. Increased atherogenic index in the general hearing loss population
  65. Prognostic role of SIRT6 in gastrointestinal cancers: a meta-analysis
  66. The complexity of molecular processes in osteoarthritis of the knee joint
  67. Interleukin-6 gene −572 G > C polymorphism and myocardial infarction risk
  68. Case Report
  69. Severe anaphylactic reaction to cisatracurium during anesthesia with cross-reactivity to atracurium
  70. Research Article
  71. Rehabilitation training improves nerve injuries by affecting Notch1 and SYN
  72. Case Report
  73. Myocardial amyloidosis following multiple myeloma in a 38-year-old female patient: A case report
  74. Research Article
  75. Identification of the hub genes RUNX2 and FN1 in gastric cancer
  76. miR-101-3p sensitizes non-small cell lung cancer cells to irradiation
  77. Distinct functions and prognostic values of RORs in gastric cancer
  78. Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy
  79. Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis
  80. Review Article
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  82. Research Article
  83. Identification of key microRNAs of plasma extracellular vesicles and their diagnostic and prognostic significance in melanoma
  84. miR-30a-3p participates in the development of asthma by targeting CCR3
  85. microRNA-491-5p protects against atherosclerosis by targeting matrix metallopeptidase-9
  86. Bladder-embedded ectopic intrauterine device with calculus
  87. Case Report
  88. Mycobacterial identification on homogenised biopsy facilitates the early diagnosis and treatment of laryngeal tuberculosis
  89. Research Article
  90. The will of young minors in the terminal stage of sickness: A case report
  91. Extended perfusion protocol for MS lesion quantification
  92. Identification of four genes associated with cutaneous metastatic melanoma
  93. Case Report
  94. Thalidomide-induced serious RR interval prolongation (longest interval >5.0 s) in multiple myeloma patient with rectal cancer: A case report
  95. Research Article
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  97. Electromyography as an intraoperative test to assess the quality of nerve anastomosis – experimental study on rats
  98. Case Report
  99. CT findings of severe novel coronavirus disease (COVID-19): A case report of Heilongjiang Province, China
  100. Commentary
  101. Directed differentiation into insulin-producing cells using microRNA manipulation
  102. Research Article
  103. Culture-negative infective endocarditis (CNIE): impact on postoperative mortality
  104. Extracorporeal shock wave therapy for the treatment of chronic pelvic pain syndrome
  105. Plasma microRNAs in human left ventricular reverse remodelling
  106. Bevacizumab for non-small cell lung cancer patients with brain metastasis: A meta-analysis
  107. Risk factors for cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage
  108. Problems and solutions of personal protective equipment doffing in COVID-19
  109. Evaluation of COVID-19 based on ACE2 expression in normal and cancer patients
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  111. Gastroenterological complications in kidney transplant patients
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  113. CXCL13 concentration in latent syphilis patients with treatment failure
  114. A novel age-biomarker-clinical history prognostic index for heart failure with reduced left ventricular ejection fraction
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  116. Clinicopathological analysis of composite lymphoma: A two-case report and literature review
  117. Trastuzumab-induced thrombocytopenia after eight cycles of trastuzumab treatment
  118. Research Article
  119. Inhibition of vitamin D analog eldecalcitol on hepatoma in vitro and in vivo
  120. CCTs as new biomarkers for the prognosis of head and neck squamous cancer
  121. Effect of glucagon-like peptide-1 receptor agonists on adipokine level of nonalcoholic fatty liver disease in rats fed high-fat diet
  122. 72 hour Holter monitoring, 7 day Holter monitoring, and 30 day intermittent patient-activated heart rhythm recording in detecting arrhythmias in cryptogenic stroke patients free from arrhythmia in a screening 24 h Holter
  123. FOXK2 downregulation suppresses EMT in hepatocellular carcinoma
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  125. Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  126. Research Article
  127. Clinical prediction for outcomes of patients with acute-on-chronic liver failure associated with HBV infection: A new model establishment
  128. Case Report
  129. Combination of chest CT and clinical features for diagnosis of 2019 novel coronavirus pneumonia
  130. Research Article
  131. Clinical significance and potential mechanisms of miR-223-3p and miR-204-5p in squamous cell carcinoma of head and neck: a study based on TCGA and GEO
  132. Review Article
  133. Hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma in noncirrhotic liver. A case report and systematic review
  134. Research Article
  135. Voltage-dependent anion channels mediated apoptosis in refractory epilepsy
  136. Prognostic factors in stage I gastric cancer: A retrospective analysis
  137. Circulating irisin is linked to bone mineral density in geriatric Chinese men
  138. Case Report
  139. A family study of congenital dysfibrinogenemia caused by a novel mutation in the FGA gene: A case report
  140. Research Article
  141. CBCT for estimation of the cemento-enamel junction and crestal bone of anterior teeth
  142. Case Report
  143. Successful de-escalation antibiotic therapy using cephamycins for sepsis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia: A sequential 25-case series
  144. Research Article
  145. Influence factors of extra-articular manifestations in rheumatoid arthritis
  146. Assessment of knowledge of use of electronic cigarette and its harmful effects among young adults
  147. Predictive factors of progression to severe COVID-19
  148. Procedural sedation and analgesia for percutaneous trans-hepatic biliary drainage: Randomized clinical trial for comparison of two different concepts
  149. Acute chemoradiotherapy toxicity in cervical cancer patients
  150. IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse
  151. NANOG regulates the proliferation of PCSCs via the TGF-β1/SMAD pathway
  152. An immune-relevant signature of nine genes as a prognostic biomarker in patients with gastric carcinoma
  153. Computer-aided diagnosis of skin cancer based on soft computing techniques
  154. MiR-1225-5p acts as tumor suppressor in glioblastoma via targeting FNDC3B
  155. miR-300/FA2H affects gastric cancer cell proliferation and apoptosis
  156. Hybrid treatment of fibroadipose vascular anomaly: A case report
  157. Surgical treatment for common hepatic aneurysm. Original one-step technique
  158. Neuropsychiatric symptoms, quality of life and caregivers’ burden in dementia
  159. Predictor of postoperative dyspnea for Pierre Robin Sequence infants
  160. Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p
  161. Analysis of expression and prognosis of KLK7 in ovarian cancer
  162. Circular RNA circ_SETD2 represses breast cancer progression via modulating the miR-155-5p/SCUBE2 axis
  163. Glial cell induced neural differentiation of bone marrow stromal cells
  164. Case Report
  165. Moraxella lacunata infection accompanied by acute glomerulonephritis
  166. Research Article
  167. Diagnosis of complication in lung transplantation by TBLB + ROSE + mNGS
  168. Case Report
  169. Endometrial cancer in a renal transplant recipient: A case report
  170. Research Article
  171. Downregulation of lncRNA FGF12-AS2 suppresses the tumorigenesis of NSCLC via sponging miR-188-3p
  172. Case Report
  173. Splenic abscess caused by Streptococcus anginosus bacteremia secondary to urinary tract infection: a case report and literature review
  174. Research Article
  175. Advances in the role of miRNAs in the occurrence and development of osteosarcoma
  176. Rheumatoid arthritis increases the risk of pleural empyema
  177. Effect of miRNA-200b on the proliferation and apoptosis of cervical cancer cells by targeting RhoA
  178. LncRNA NEAT1 promotes gastric cancer progression via miR-1294/AKT1 axis
  179. Key pathways in prostate cancer with SPOP mutation identified by bioinformatic analysis
  180. Comparison of low-molecular-weight heparins in thromboprophylaxis of major orthopaedic surgery – randomized, prospective pilot study
  181. Case Report
  182. A case of SLE with COVID-19 and multiple infections
  183. Research Article
  184. Circular RNA hsa_circ_0007121 regulates proliferation, migration, invasion, and epithelial–mesenchymal transition of trophoblast cells by miR-182-5p/PGF axis in preeclampsia
  185. SRPX2 boosts pancreatic cancer chemoresistance by activating PI3K/AKT axis
  186. Case Report
  187. A case report of cervical pregnancy after in vitro fertilization complicated by tuberculosis and a literature review
  188. Review Article
  189. Serrated lesions of the colon and rectum: Emergent epidemiological data and molecular pathways
  190. Research Article
  191. Biological properties and therapeutic effects of plant-derived nanovesicles
  192. Case Report
  193. Clinical characterization of chromosome 5q21.1–21.3 microduplication: A case report
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Heruntergeladen am 8.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2020-0041/html
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