Startseite The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
Artikel Open Access

The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer

  • Shuo Li , Qi-Li Zhang und Rui-Jun Guo EMAIL logo
Veröffentlicht/Copyright: 8. November 2023

Abstract

To determine whether ultrasound (US) features of breast cancer are associated with Breast Imaging and Reporting Data System molecular subtype, histologic grade, and hormone receptor status as well as to assess the predictive value of these features. Retrospective analysis of the medical records of 220 consecutive patients with invasive breast cancer was reviewed according to the PIK3CA-mutated molecular tumor subtype. US findings of all patients were analyzed. Breast tumors harboring a PIK3CA-mutation were large and exhibited liquefied necrosis and posterior echo attenuation in the nodule. Moreover, such tumors were lobulated and calcified. The aspect ratio of the PIK3CA-mutant was more likely >1. The average nodule elasticity (7.479 ± 0.993 m/s) was measured using US shear wave elastography. Microcalcification was easier to detect inside the nodule using a fluorescence technique. Measurement of the nodule blood flow spectrum showed that the internal blood flow resistance index of nodules was lower than that of other types of breast cancer. The sonographic features of PIK3CA-mutated breast cancers were strongly associated with extensive and liquefied necrosis. The ability to predict molecular subtypes, particularly using US to detect the triple-negative subtype, may play an important role in early management and treatment.

1 Introduction

Global cancer data released in 2020 by the World Health Organization International Cancer Research Institute included 2,261,419 new cases of breast cancer and 684,996 [1] deaths; including 416,471 new cases of breast cancer and 117,174 deaths in China (https://gco.iarc.fr/today/home). During the past 20 years, the development of experimental and clinically approved breast cancer-targeting drugs has been progressing rapidly. Examples include endocrine therapy, poly(ADP-ribose) polymerase (PARP) inhibitors (referred to as “PARPi”), phosphatidylinositol-3-kinase PI3K inhibitors, and human epidermal growth factor receptor-2 (HER2) inhibitors, which achieve good therapeutic effects [26]. Moreover, despite intensive interest in immunotherapy, it does not effectively treat advanced breast cancer [6,7]. Therefore, targeted therapy continues to play an important role in breast cancer chemotherapy.

The PI3Ka/mammalian target of rapamycin (mTOR) pathway is frequently dysregulated in cancer because of mutation, amplification, or both, of the genes such as those encoding the PI3K catalytic subunits p110a (PIK3CA) and p110b (PIK3CB), the PI3K regulatory subunit p85a (PIK3R1), AKT1-3, and the phosphatidylinositol-3,4,5 trisphosphate (PIP3) phosphatases PTEN and INPP4B [7,8]. PIK3CA mutations induce a transformed phenotype, including growth factor- and anchorage-independent growth, resistance to anoikis, and drug resistance. Mutations in PIK3CA are present in 28–46% of people with hormone receptor (HR)-positive  – HER2-negative advanced breast cancer [8,9].

Alpelisib (BYL719; Novartis Pharma AG, Basel, Switzerland) is an orally administered, selective inhibitor of p110a [3,4]. Notably, more patients still received treatment in the alpelisib plus fulvestrant arm of clinical trials, particularly considering the poor prognosis of these patients with PIK3CA-mutated disease who experience shorter survival [69].

Ultrasonography is the first choice for screening for breast cancer. The first aim of the ultrasound (US) examination is to identify benign and malignant nodules. Furthermore, with the rise of targeted therapy, it is critically important to identify the characteristics of PIK3CA mutations in US images of breast cancer. Therefore, our Radiology Department faces the most urgent key scientific problems such as analyses of the characteristics of US images of different genotypes of breast cancer and implementation of early diagnosis and treatment. This will be of great practical significance to expand the scope of clinical application of drugs and to lengthen patients’ survival rates.

Therefore, the purpose of the present study was to determine whether the US features of breast cancer are associated with Breast Imaging and Reporting Data System (BI-RADS) molecular subtype, histologic grade, and HR status as well as their abilities to predict patients’ outcomes.

2 Methods

The US features of 220 consecutive patients with primary invasive breast cancer, who were treated and followed at our breast cancer center between November 2011 and August 2013, were retrospectively evaluated using an electronic database. Of the 220 patients, we excluded 19 with incomplete data and bilateral and recurrent breast cancer. Thirty-three of 201 (16.4%) invasive breast cancers were multifocal, and in these cases, the largest lesion was evaluated. All patients had histologically proven breast cancer and molecular subtypes revealed by analyses of surgical specimens. Patients in the PIK3CA-mutant and non-mutant cohorts were randomized.

The Ethics Committee of the Beijing Chaoyang Hospital approved this study (2021-Ke-704). Informed consent from patients with PIK3CA-mutated breast cancer was not required by the Ethics Committee for this retrospective study.

2.1 Ultrasonography

US scans were performed using a 13–5 MHz linear transducer (VF13–5 Acuson Antares, Siemens, Erlangen, Germany), and the data were evaluated by two radiologists specializing in breast cancer with ≥5 years’ experience performing breast imaging. Both radiologists were uninformed regarding the histopathology results. One radiologist assessed the US images of each tumor from the image archiving and communication system and soft copy images, and the second radiologist was consulted if a case was unclear. All US exams were performed by radiologists, and multiple images were recorded.

The database records of 201 consecutive patients with invasive breast cancer were reviewed according to the molecular subtype of PIK3CA-mutated disease. Sonographic tumor sizes were classified as ≤10 mm3 and >10 mm3; aspect ratios ≤1 and >1; internal echo as low, medium, and high; and ultrasonic shear wave elasticity (USWE) microcalcification as yes or none. Tumor margins were classified as circumscribed or non-circumscribed. The posterior acoustic features were divided into categories as follows: shadowing, enhancement, no change, and mixed pattern. Two senior attending physicians jointly evaluated the images. If there was disagreement, the chief physician was consulted.

2.2 Statistical analysis

SPSS 24.0 software (IBM, Chicago, IL, USA) was used for statistical analysis. Normally distributed clinical quantitative parameters are expressed as the mean ± standard deviation and compared using the Student’s t test, while non-normally distributed variables are expressed as the median (interquartile range) and analyzed by using the Wilcoxon signed rank test. Data for categorical variables are expressed as numbers (percentages), and the chi-square test was used. Univariate and multivariate logistic regression models were used to analyze the relationship between the classifications. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of the C-statistic that best correlated with the patient’s prognosis. The Kaplan–Meier method was used to estimate overall survival, and P < 0.05 indicates a statistically significant difference.

3 Results

Table 1 shows the tumor characteristics and US imaging features of patients included in the study. The mean age at diagnosis of patients with non-mutated tumors was 48 ± 15 years (range, 23–83 years), and the ultrasonographic mean tumor size was 22 ± 14.1 mm. Histologic grade was 1 or 2 in 73 patients (36.3%) and grade 3 in 128 patients (63.7%). Among 201 patients with invasive breast cancer, the molecular subtype was luminal A in 58 (28.9%), luminal B in 99 (49.3%), HER2-positive in 18 (9.0%), and triple-negative in 26 (12.9%). The research flow chart is shown in Figure 1.

Table 1

Patients’ tumor characteristics and US imaging features

Contents Independent variables, n (%)
Dependent variables PIK3CA-mutant (n = 81) Non-mutant (n = 120) F P
Age (years) 11.733 0.001*
≤50 33 81
>50 48 39
Tumor grade 118.557 <0.001*
1 or 2 25 110
3 56 10
Sonographic tumor size (mm3) 1.767 0.185
≤10
>10
Margins 157.757 <0.001*
Circumscribed
Non-circumscribed
Aspect ratio 117.613 <0.001*
≤1 8 90
>1 73 30
Internal echo (low = 0, medium = 1, high = 2) 24.465 <0.001*
0 0 52
1 56 40
2 25 28
Posterior acoustic features 0.071 0.790
No change
Enhancement
Shadowing
Microcalcification 25.214 <0.001*
None 16 63
Yes 65 57
BI-RADS 0.004 0.948
≤3
>4
USWE 68.172 <0.001*
x ± s (m/s) 7.479 ± 0.993 4.435 ± 2.402

Quantitative data are expressed as the mean ± standard deviation and categorical variables are expressed as number (percentage). *Statistically significant.

Figure 1 
               Research flow chart.
Figure 1

Research flow chart.

3.1 US imaging features of PIK3CA-mutated tumors

The breast tumors of patients with mutated PIK3CA were large and exhibited liquefied necrosis. There was posterior echo attenuation in the nodule, and the tumors were lobulated and calcified. The aspect ratios of PIK3CA-mutated tumors were more likely ≥1. The average nodule elasticity was 7.479 ± 0.993 m/s, which was measured using USWE. Microcalcification was more readily detected inside the nodule when a fluorescence technique was employed. Measurement of the nodule blood flow spectrum showed that the internal blood flow resistance index of nodules was lower than that of other types of breast cancers (Figure 2).

Figure 2 
                  US imaging features of PIK3CA-mutated breast tumors. (a) Large nodules with liquefaction necrosis. (b) Echo attenuation behind nodules. (c) Nodules lobulated with inner calcification. (d) Nodule aspect ratio >1. (e) Elasticity measurements of nodules through shear-wave techniques. (f) Intranodal microcalcifications detected using a fluorescence technique (microcalcifications in blue, white light). (g) Nodular blood-flow spectrum measurements show that the intranodular blood flow resistance index is lower than those of other types of breast cancer.
Figure 2

US imaging features of PIK3CA-mutated breast tumors. (a) Large nodules with liquefaction necrosis. (b) Echo attenuation behind nodules. (c) Nodules lobulated with inner calcification. (d) Nodule aspect ratio >1. (e) Elasticity measurements of nodules through shear-wave techniques. (f) Intranodal microcalcifications detected using a fluorescence technique (microcalcifications in blue, white light). (g) Nodular blood-flow spectrum measurements show that the intranodular blood flow resistance index is lower than those of other types of breast cancer.

We adjusted the factors as follows: age, grade, echoic, margins, aspect ratio, microcalcification, and USWE. Multivariate logistic analysis (Table 2) revealed significant differences associated with age (coefficient: 0.336; 95% CI: 0.253–0.419; P < 0.0001), grade (coefficient: 0.281; 95% CI: 0.185–0.376; P < 0.0001), echoic (coefficient: 0.113; 95% CI: 0.185–0.376; P < 0.0001), margins (coefficient: 0.286; 95% CI: 0.165–0.407, P < 0.0001), aspect ratio (coefficient: 0.250; 95% CI: 0.165–0.407; P = 0.001), microcalcification (coefficient: 0.147; 95% CI: 0.274–0.020; P = 0.024), and USWE (coefficient: 0.051; 95% CI: 0.034–0.069; P < 0.0001).

Table 2

Logistic analysis results of features of PIK3CA-mutated breast tumors

Contents Coefficients Std. error t Stat P-value 95% CI
Intercept 0.447 0.063 7.137 0.000 0.571–0.324
Age 0.336 0.042 7.954 0.000 0.253–0.419
Grade 0.281 0.048 5.795 0.000 0.185–0.376
Internal echo (low = 0, medium = 1, high = 2) 0.113 0.029 3.914 0.000 0.056–0.171
Margins (circumscribed = 0, non-circumscribed = 1) 0.286 0.061 4.664 0.000 0.165–0.407
Aspect ratio (0: <1, 1: >1) 0.250 0.078 3.222 0.001 0.097–0.403
Microcalcification (0: none, 1: yes) 0.147 0.064 2.276 0.024 0.274–0.020
USWE 0.051 0.009 5.926 0.000 0.034–0.069

ROC analysis yielded area under the curve (AUC) values as follows: grade = 0.835 (std. error: 0.01413; 95% CI: 0.9277–0.9831; P < 0.0001), margins = 0.832 (std. error: 0.02781; 95% CI: 0.8296–0.938; P < 0.0001), aspect ratio = 0.803 (std. error: 0.02726; 95% CI: 0.5193–0.626; P = 0.0083), microcalcification = 0.665 (std. error: 0.02683; 95% CI: 0.5610–0.6662; P < 0.0001), and USWE = 0.797 (std. error: 0.02381; 95% CI: 0.6851–0.7784; P < 0.0001) (Figures 3 and 4).

Figure 3 
                  US analysis of PIK3CA-mutated and non-mutated tumors. (a) Comparison of USWE between PIK3CA-mutated and non-mutated tumors. (b) ROC curve of pathological grade, margin, aspect ratio, microcalcification, and USWE.
Figure 3

US analysis of PIK3CA-mutated and non-mutated tumors. (a) Comparison of USWE between PIK3CA-mutated and non-mutated tumors. (b) ROC curve of pathological grade, margin, aspect ratio, microcalcification, and USWE.

Figure 4 
                  ROC curve-predicted values. AUC: 0.959 (std. error: 0.019; 95% CI: 0.923–0.995; P = 0.000).
Figure 4

ROC curve-predicted values. AUC: 0.959 (std. error: 0.019; 95% CI: 0.923–0.995; P = 0.000).

4 Discussion

In the present study, we determined whether the US features of breast cancer were associated with the BI-RADS molecular subtype, histologic grade, and HR status. Furthermore, we assessed the predictive value of these features. Our findings show that the sonographic features of PIK3CA-mutated breast tumors were obviously associated with large tumors and liquefied necrosis, suggesting the ability of US to predict molecular subtypes; particularly the triple-negative subtypes may play an important role in early management and treatment.

Breast cancer is a heterogeneous disease with different histopathological and associated biological characteristics [13]. Over the past few decades, treatment of breast cancer has entered the molecular, genomics, and proteomics levels, which has improved treatment efficacy to lengthen the survival of patient with breast cancer [46]. Previously, breast cancer was treated as a disease without a classification. In 2000, the advent of molecular genetic technology made possible high-resolution molecular typing, culminating in personalized treatment [79]. The 70-gene detection MammaPrint microarray was approved for clinical use in China, representing a very important milepost [1,8]. The MammaPrint “70 gene detection” technique provides an important prognostic tool for ERPR-positive and HER2-negative patients with breast cancer, and the score is calculated at RNA transcriptional level [714].

Molecular biological studies reveal the heterogeneity of breast cancer, which help to obtain more precise prognostic and prediction information [10,11]. Therefore, the molecular typing of breast cancer includes the phenotypes as follows: luminal A, luminal B, Her2 overexpression, and triple-negative breast cancer. Patients in the present study had luminal A and B molecular subtypes (78%).

Breast US has become an effective method to identify benign and malignant lesions, particularly those of young women with dense breast tissue [1012]. Although many studies focus on the ultrasonographic findings of breast cancer grading, studies on the relationship between tumor subtypes are unavailable [3,8], and imaging data on the identification of molecular subtypes are unavailable as well. Compared with the HR-negative state, HR-positive tumors are more likely to have uncertain margins. In the present study, multivariate analysis revealed significant differences associated with age, grade, echoic, margins, aspect ratio, and microcalcification.

Previously, most malignant breast tumors examined using US were thought to have posterior acoustic shadows with blurry edges [13,14]. However, it is now well known that many tumors may exhibit variable posterior acoustic features. For example, recent studies show that a clear margin and post-enhancement are more likely to represent a higher level of tumor and receptor-negative status [13,15,16]. Our results are consistent with these findings, particularly the statistically significant correlation between a clear margin and post-enhancement.

In the present study, histologic grade was 1 or 2 in 73 patients and grade 3 in 128 patients. Among 201 patients with invasive breast cancer, the molecular subtypes were luminal A in 58, luminal B in 99, HER2 in 18, and triple-negative in 26. Tumors with HR-positive status (n = 154) were more likely to have non-circumscribed margins (n = 108), and tumors with HR-negative status (n = 47) were more likely to have circumscribed margins (n = 32). Circumscribed margins also are among the most frequent alterations in solid tumors, identified in the cancers as follows: 42–55%, endometrial; 24%, cervical; 18%, colorectal, 13%, head and neck; and 12%, ovarian. Targeting the PI3K/mTOR pathway therefore may be particularly effective in cancers that signal through PI3Ka [1719]. Further studies with larger sample size are needed to investigate the differences in US features among patients with different expression levels of HER2 and HR.

The results of the present study showed that sonographic features of PIK3CA-mutated tumors were significantly associated with large and liquefied necrosis. Here we show posterior echo attenuation and microcalcification in the nodule and that the average nodule elasticity was 7.479 ± 0.993 m/s measured using USWE. Furthermore, measurement of the nodule blood flow spectrum reveals a lower internal blood flow resistance index of nodules compared with those of other types of breast cancer. The ability use US to predict molecular subtypes, particularly the triple-negative subtype, may play an important role in optimizing early management and treatment. Large multi-center studies are required to confirm these findings.

Acknowledgement

Not applicable.

  1. Funding information: The authors state no funding involved.

  2. Author contributions: S.L.: writing the draft of the manuscript, analysis and interpretation of data, administrative, technical, or material support. R.G.: conception and design; Q.Z.: analysis and interpretation of data, study supervision.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Data availability statement: The data used and analyzed during the current study are available from the corresponding authors on reasonable request.

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Received: 2022-03-27
Revised: 2023-04-19
Accepted: 2023-05-05
Published Online: 2023-11-08

© 2023 the author(s), published by De Gruyter

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

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  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
Heruntergeladen am 10.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2023-0725/html
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