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Potential Role of MicroRNA-375 as Biomarker in Human Cancers Detection: A Meta-Analysis.

ABSTRACT: The association between circulating microRNA-375 (miR-375) expression and cancers has been studied; however, the results are inconsistent. We searched PubMed, Embase, and Web of Science for studies concerning the diagnostic value of miR-375 for cancer. The bivariate meta-analysis model was employed to summarize sensitivity, specificity, and diagnostic odds ratio (DOR) for miR-375 in the diagnosis of cancer. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were also used to check the overall test performance. A total of 645 cancer patients and 421 cancer-free individuals from 12 studies were contained in this meta-analysis. The summary estimates revealed that the pooled sensitivity was 78% (95% confidence interval (CI): 64%-87%), the specificity was 74% (95% CI: 62%-84%), the DOR was 10.04 (95% CI: 6.01-16.77), and the AUC was 0.82 (95% CI: 0.79-0.85). In addition, we found that the diagnostic effect of miR-375 varies according to the race and cancer type. Our data suggest that miR-375 profiling has a potential to be used as a screening test for cancers but the specific race and cancer should be considered. More studies on the diagnostic value of miR-375 for cancer are needed in the future.

SUBMITTER: Yan J

PROVIDER: S-EPMC5702930 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Deubiquitinase OTU domain containing 4 (OTUD4) is initially identified as a K48-specific deubiquitinase and plays an important role in DNA damage repair signaling transduction. However, the expression level, prognostic role, biological function and mechanism of OTUD4 in multiple human cancers are unclear. Methods:GEPIA online (http://gepia.cancer-pku.cn/; The Cancer Genome Atlas (TCGA) database) was used to analyze the mRNA expression of OTUD4 in multiple human cancers. Kaplan-Meier plotter (KM plotter) database and TCGA database were used to evaluate the prognostic value of OTUD4 expression in multiple human cancers. MTT, Transwell and 3D culture assays were used to detect the role of OTUD4 in breast, liver and lung cancer cells. The correlation between OTUD4 and apoptosis signaling pathway and AKT signaling pathway was analyzed by Gene set enrichment analysis (GSEA). Results:OTUD4 mRNA expression is significantly downregulated in multiple human cancer tissues. Survival analysis establishes that the downregulation of OTUD4 predicts poor prognosis in many solid tumors, including breast invasive carcinoma (BRCA), esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and ovarian serous cystadenocarcinoma (OV). Furthermore, overexpression of OTUD4 could inhibit tumor cell proliferation, migration and invasion of breast, liver and lung cancer cells through inhibiting the AKT signaling pathway. Conclusion:This study found that OTUD4 may be a potential predictive factor for several human cancers and a tumor suppressor for breast, liver and lung cancer. The overexpression of OTUD4 restrained proliferation, migration and invasion of human breast, liver and lung cancer cells through promoting cancer cells apoptosis and inhibiting AKT signaling pathway. Notably, our results indicated that OTUD4 could be a useful biomarker for the prognosis of human cancers and a potential molecular target for diagnosis and treatment of breast, liver and lung cancer.

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Potential Role of MicroRNA-375 as Biomarker in Human Cancers Detection: A Meta-Analysis.

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