The potent potential of MFAP2 in prognosis and immunotherapy of triple-negative breast cancer.

BACKGROUNDS: Microfibril-associated protein 2 (MFAP2) is a protein presenting in the extracellular matrix that governs the activity of microfibrils through its interaction with fibrillin. While the involvement of MFAP2 in metabolic disorders has been documented, its expression and prognostic significance in triple-negative breast cancer (TNBC) remain unexplored. METHODS: We acquired datasets pertaining to breast cancer (BC) from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Next, a Venn diagram was used to identify the differentially expressed genes (DEGs). The DEGs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), immune and survival analysis. The expressions of MFAP2, PD-1 and PD-L1 were examined by immunohistochemistry and western blot and their relationship with clinical pathological parameters were analyzed by clinical specimen samples from patients with TNBC. Tumor Immune Estimation Resource (TIMER, https://cistrome.shinyapps.io/timer/ ) was adopted to calculate the immune infiltration level of TNBC. The link between gene expression and tumor mutational burden (TMB) was described using Spearman's correlation analysis. RESULTS: We identified 66 differentially expressed genes (DEGs) that were up-regulated. Among these DEGs, MFAP2 was found to be overexpressed in TNBC and was associated with a lower probability of survival. This finding was confirmed through the use of immunohistochemistry and western blot techniques. Additionally, MFAP2 was found to be related to various pathological parameters in TNBC patients. Mechanistically, gene set enrichment analysis (GSEA) revealed that MFAP2 primarily influenced cellular biological behavior in terms of epithelial mesenchymal transition, glycolysis, and apical junction. Notably, MFAP2 expression was positively correlated with the abundance of macrophages, while a negative correlation was observed with the abundance of B cells, CD4 + T cells, CD8 + T cells, neutrophils and dendritic cells through immune analysis. Furthermore, it was observed that MFAP2 displayed a negative correlation not only with tumor mutational burden (TMB), a recognized biomarker for PD-1/PD-L1 immunotherapy, but also with PD-L1 in samples of TNBC. CONCLUSION: MFAP2 may be an important prognostic biomarker for TNBC, as well as a viable target for immunotherapy in this disease.

Association of lipid-modifying therapy with risk of obstructive sleep apnea: A drug-target mendelian randomization study.

BACKGROUND: Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA. METHODS: A drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed. The MR analyses used summary-level data of genome wide association studies (GWAS). Primary MR analysis was conducted using inverse-variance-weighted (IVW) method. Sensitivity analysis was performed using weighted median (WM) and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. RESULTS: Genetically proxied low-density lipoprotein cholesterol (LDL-C)-lowering effect of cholesteryl ester transfer protein (CETP) was associated with reduced risk of OSA (odds ratio [OR] =0.75, 95% confidence interval [CI]: 0.60-0.94, false discovery rate [FDR] q value = 0.046). A significant MR association with risk of OSA was observed for CETP expression in subcutaneous adipose tissue (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049), lung (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049) and small intestine (OR = 0.96, 95%CI: 0.93-1.00, FDR q value = 0.049). No significant effects of high-density lipoprotein cholesterol (HDL-C)-raising effect of CETP inhibition, LDL-C-lowering and triglycerides-lowering effect of other drug targets on OSA risk were observed. CONCLUSIONS: The present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations.

GEFT aberrant expression in soft tissue sarcomas.

BACKGROUND: Guanine nucleotide exchange factor T (GEFT) exhibits high amplification level using high-resolution array comparative genomic hybridization in rhabdomyosarcoma. The overexpression rate of GEFT protein is higher in rhabdomyosarcoma than in normal striated muscle tissues. This study evaluated the aberrant expression of GEFT in multiple subtypes of soft tissue sarcoma (STS) and compared the differences in clinical pathology, histological feature and expression levels of GEFT protein and mRNA between chromosomal translocation-associated sarcomas (CTAS) and non-chromosomal translocation-associated sarcomas (NCTAS). METHODS: GEFT protein expression was detected using immunohistochemistry (IHC) and tissue microarrays. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to detect the expression of GEFT mRNA. RESULTS: The rates of GEFT positive expression (196/219, 89.50%) and overexpression (113/219, 51.60%) were higher in multiple subtypes of STS than in normal striated muscle tissues. The rates of GEFT positive expression and overexpression in all subtypes of STS detected were significantly higher than that in the controls. No difference of GEFT expression was detected between CTAS and NCTAS. CONCLUSIONS: The abnormal expression of GEFT exists in various subtypes of STS, which may play an important role in tumorigenesis of STS.

Diagnosis and Prognostic Significance of c-Met in Cervical Cancer: A Meta-Analysis.

OBJECTIVE: A meta-analysis was conducted to analyze c-Met expression in cervical cancer. METHODS: Articles related to our study were retrieved from PubMed, Elsevier, and China National Knowledge Infrastructure. State 12.0 was used for literature review, data extraction, and meta-analysis. The random-effects model and fixed-effects model were utilized to pool the relative ratio based on the heterogeneity test in the meta-analysis. RESULTS: Nine studies that include data of 685 cervical carcinoma tissues were analyzed. However, three studies did not thoroughly discuss c-Met expression in nonneoplastic cervical tissue; thus, only six studies involving 364 patients and 228 nonneoplastic cervical tissues were included in the review. c-Met expression was higher in cervical cancer (60.99%) than in nonneoplastic cervical tissue (19.74%). Cervical carcinoma, cervical intraepithelial neoplasm, and normal cervical tissue were also examined. Results showed that increasing malignancy resulted in elevated c-Met expression. The relationship between c-Met expression and clinicopathologic features was also evaluated. c-Met expression correlated with disease-free survival, lymph node involvement, and lymphovascular space invasion. No statistical difference was observed between c-Met expression and other clinicopathological factors. CONCLUSIONS: c-Met is a potential diagnostic and prognostic indicator of cervical cancer.

Clinicopathological Significance of RhoA Expression in Digestive Tract Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: RhoA protein expression has been reported in different types of cancer. We performed an up-to-date meta-analysis to evaluate the clinicopathological characteristics of RhoA protein expression in patients with gastrointestinal cancer. METHODS: We searched in several databases, including MEDLINE (PubMed) and China National Knowledge Infrastructure, to identify studies examining the association between RhoA protein and cancer. The quality of the included studies was assessed. Cochrane Collaboration's Software Review Manager 5.3 was utilized to test the heterogeneity, overall effect, and publication bias of the combined studies. The reported odds ratio and 95% confidence interval (CI) were calculated by using fixed and random effects models depending on the heterogeneity of the included studies. RESULTS: A total of 15 studies met the inclusion criteria of the meta-analysis. RhoA expression was significantly higher in gastrointestinal cancer than in normal tissues. RhoA protein expression in digestive system neoplasms was significantly associated with tumor clinical staging, metastatic status and differentiated degree. However, no association with gender was found. RhoA mRNA expression was no associated with clinicopathological significance. CONCLUSIONS: Current evidence supports the conclusion that RhoA expression is associated with clinical staging, metastatic status, and differentiated degree in digestive system neoplasms. RhoA expression may play an important role in the carcinogenesis and metastasis of gastrointestinal cancer.

Clinicopathological significance of Notch1 expression in cervical cancer patients: a meta-analysis.

AIM: Notch1 expression remains incompatible and contradictory with previous findings on cervical cancer. The purpose of this study is to evaluate the association between Notch1 and cervical cancer. METHODS: Available studies were searched from diverse databases and Review Managers 5.3 software was used to perform analysis. RESULTS: A total of 798 samples were included in this meta-analysis. The Notch1 expression in cancer tissues was higher than that in precancer (p = 0.0003) and normal tissues (p < 0.02). However, the difference of Notch1 expression between cancer cases and precancer cases has no statistical significance (p = 0.35). Moreover, lymph node metastasis (p = 0.02) was associated with higher Notch1 expression in cervical cancer. CONCLUSION: Notch1 over-expression indicated aggressive biological behaviors.

Meta-analysis of downregulated E-cadherin as a poor prognostic biomarker for cervical cancer.

AIM: This meta-analysis was conducted to evaluate the diagnostic and prognostic functions of E-cadherin expression in cervical cancer. METHODS: PubMed and other databases were searched for articles associated with E-cadherin and cervical cancer. These articles were published before June 2015 and written in English or Chinese. Random-effects model was used to pool odds ratios on the heterogeneity test in the meta-analysis. RESULTS: All of 20 studies were analyzed, in which 522 (42.6%) subjects exhibited reduced E-cadherin expression. Evaluation of clinicopathologic features showed that the downregulation of E-cadherin was related to the overall survival, clinicopathological parameters and age. CONCLUSION: Downregulation of E-cadherin in cervical cancer patients showed poor overall survival. Therefore, E-cadherinmay be a metastasis-suppressor gene in cervical cancer.

Aggressive angiomyxoma of the liver: a case report.

Aggressive angiomyxoma (AAM) is a rare benign mesenchymal tumor that occurs almost exclusively in the soft tissues of the pelvis and perineum. Very few cases of AAM occurring outside these regions have been reported. The present report presents a case of AAM originating from the liver of a 50-year-old female patient. Tumor resection was performed, and pathological examination revealed microscopic features that were characteristic of AAM. Histopathological examination showed that the tumor was composed of scattered spindle-or stellate-shaped cells with thick-walled blood vessels lying in a myxoid stroma. Immunohistochemically, the tumor cells stained positively for CD34, vimentin, and actin. In this paper, we also discuss the differential diagnosis of AAM. To the best of our knowledge, this study is the first to report a case of AAM originating from the liver.