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Prognostic and diagnostic significance of circRNAs expression in hepatocellular carcinoma patients: A meta-analysis.

ABSTRACT: Circular RNAs (circRNAs) as novel biomarkers are widely investigated in various cancers. The aim of our study was to reveal the clinicopathological, prognostic, and diagnostic features of circRNAs in human hepatocellular carcinoma (HCC). A systematical search was conducted on PubMed, Scopus, Web of Science (WOS), EMBASE, and the Cochrane Library databases. Eligible studies reporting on the association among circRNAs and clinicopathological, prognostic, diagnostic values of HCC patients were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to assess clinicopathological parameters, sensitivity, and specificity, and hazard ratios (HRs) were to evaluate overall survival (OS). 17 eligible studies which included 7 for clinicopathological features, 10 for prognosis, and 8 for diagnosis were in our study. As for clinicopathological parameters, high expression of oncogenic circRNAs had a significant association with poor clinicopathological features and tumor-suppressor circRNAs proved the contrary. In terms of the prognostic values, oncogenic circRNAs had a negative influence on overall survival (OS: HR = 3.39, 95%Cl: 2.59-4.19), and high expression of tumor-suppressor circRNAs was relevant to improved survival outcomes (OS: HR = 0.46, 95%Cl: 0.37-0.56). The pooled diagnostic outcomes indicated an area under the curve (AUC) of 0.84, with sensitivity of 82% and specificity of 72% in discriminating HCC from controls. Our study indicates that circRNAs may be important biomarkers for prognostic and diagnostic values of HCC.

SUBMITTER: Huang X

PROVIDER: S-EPMC6434206 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Prognostic and diagnostic significance of circRNAs expression in hepatocellular carcinoma patients: A meta-analysis.

Huang Xin X Zhang Weiyue W Shao Zengwu Z

Cancer medicine 20190128 3

Circular RNAs (circRNAs) as novel biomarkers are widely investigated in various cancers. The aim of our study was to reveal the clinicopathological, prognostic, and diagnostic features of circRNAs in human hepatocellular carcinoma (HCC). A systematical search was conducted on PubMed, Scopus, Web of Science (WOS), EMBASE, and the Cochrane Library databases. Eligible studies reporting on the association among circRNAs and clinicopathological, prognostic, diagnostic values of HCC patients were incl ...[more]

PMID: 30693679

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Project description:BackgroundsHepatocellular Carcinoma (HCC) is one of the most common malignancy of liver and HCC-related morbidity and mortality remains at high level. Researchers had investigated whether and how reduced E-cadherin expression impacted the prognosis of patients with HCC but the results reported by different teams remain inconclusive.MethodsA systematic literature search was performed in all available databases to retrieve eligible studies and identify all relevant data, which could be used to evaluate the correlation between reduced E-cadherin expression and clinicopathological features and prognosis for HCC patients. A fixed or random effects model was used in this meta-analysis to calculate the pooled odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI).ResultsTotal 2439 patients in thirty studies matched the selection criteria. Aggregation of the data suggested that reduced E-cadherin expression in HCC patients correlated with poor 1-, 3- and 5-year overall survival. The combined ORs were 0.50 (n = 13 studies, 95% CI: 0.37-0.67, Z = 4.49, P<0.00001), 0.39 (n = 13 studies, 95% CI: 0.28-0.56, Z = 5.12, P<0.00001), 0.40 (n = 11 studies, 95% CI: 0.25-0.64, Z = 3.82, P = 0.0001), respectively. Additionally, the pooled analysis denoted that reduced E-cadherin expression negatively impacts recurrence-free survival (RSF) with no significant heterogeneity. The pooled ORs for 1-, 3- and 5- year RSF affected by down-regulated E-cadherin were 0.73 (n = 6 studies, 95% CI: 0.54-1.00, Z = 1.95, P = 0.05), 0.70 (n = 6 studies, 95% CI: 0.52-0.95, Z = 2.32, P = 0.02), 0.66 (n = 5 studies, 95% CI: 0.48-0.90, Z = 2.64, P = 0.008). And what's more, reduced E-cadherin expression tended to be significantly associated with metastasis (OR = 0.31, 95% CI: 0.16-0.60, Z = 3.50, P = 0.0005), vascular invasion (OR = 0.76, 95% CI: 0.59-0.98, Z = 2.14, P = 0.03), advanced differentiation grade (OR = 0.31, 95% CI: 0.21-0.45, Z = 6.04, P<0.00001) and advanced TMN stage (T3/T4 versus T1/T2) (OR = 0.61,95% CI:0.38-0.98, Z = 2.05, P = 0.04).ConclusionsReduced E-cadherin expression indicates a poor prognosis for patients with HCC, and it may have predictive potential for prognosis of HCC patients.

Project description:IntroductionWD repeat domain phosphoinositide-interacting protein 3 (WIPI3) is a member of the WIPI protein family, autophagy marker, that is associated with the malignant progression of various human cancers, but its role in hepatocellular carcinoma (HCC) is still unclear.Materials and methodsFirstly, we collected the mRNA expression of WIPI3 in HCC through the platform of Oncomine, as well as the DNA copy number variations (CNVs), and verified it on human HCC cell line and the GEO database. Then, the subgroups and prognosis of HCC were performed by the UALCAN web tool. The mutation of WIPI3 was analyzed by cBioPortal. The coexpression of WIPI3 in HCC was identified from the LinkedOmics database, and function enrichment analysis was done using the LinkFinder module in LinkedOmics. Coexpression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules; both of them were visualized by the Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) by using the UCSC Xena browser.ResultsThe results indicated that WIPI3 was frequently overexpressed in HCC, which could lead to a poor prognosis through the Kaplan-Meier (KM) analysis. Moreover, there existed mutations of WIPI3 in HCC, and the prognosis of WIPI3-altered group was significantly poor based on KM plotter data. Coexpression analysis showed that the coexpression gene of WIPI3 was associated with cell cycle and spliceosome. Further analysis suggested that WIPI3 and eukaryotic translation initiation factor 4A3 (EIF4A3) coordinately regulated the cancer cell cycle by spliceosome as a result of the strong positive correlation between them.ConclusionIn summary, WIPI3 is constantly overexpressed in HCC tissues, resulting in a poor prognosis; therefore, we can identify it as an effective target for the treatment of HCC.

Project description:Background Circular RNAs (circRNAs) are types of endogenous noncoding RNAs produced by selective splicing that are expressed highly specifically in various organisms and tissues and have numerous clinical implications in the regulation of cancer development and progression. Since circRNA is resistant to digestion by ribonucleases and has a long half-life, there is increasing evidence that circRNA can be used as an ideal candidate biomarker for the early diagnosis and prognosis of tumors. In this study, we aimed to reveal the diagnostic and prognostic value of circRNA in human pancreatic cancer (PC). Methods A systematic search for publications from inception to 22 July 2022 was conducted on Embase, PubMed, Web of Science (WOS), and the Cochrane Library databases. Available studies that correlated circRNA expression in tissue or serum with the clinicopathological, diagnostic, and prognostic values of PC patients were enrolled. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to evaluate clinical pathological characteristics. Area under the curve (AUC), sensitivity, and specificity were adopted to assess diagnostic value. Hazard ratios (HRs) were utilized to assess disease-free survival (DFS) and overall survival (OS). Results This meta-analysis enrolled 32 eligible studies, including six on diagnosis and 21 on prognosis, which accounted for 2,396 cases from 245 references. For clinical parameters, high expression of carcinogenic circRNA was significantly associated with degree of differentiation (OR = 1.85, 95% CI = 1.47–2.34), TNM stage (OR = 0.46, 95% CI = 0.35–0.62), lymph node metastasis (OR = 0.39, 95% CI = 0.32–0.48), and distant metastasis (OR = 0.26, 95% CI = 0.13–0.51). As for clinical diagnostic utility, circRNA could discriminate patients with pancreatic cancer from controls, with an AUC of 0.86 (95% CI: 0.82–0.88), a relatively high sensitivity of 84%, and a specificity of 80% in tissue. In terms of prognostic significance, carcinogenic circRNA was correlated with poor OS (HR = 2.00, 95% CI: 1.76–2.26) and DFS (HR = 1.96, 95% CI: 1.47–2.62). Conclusion In summary, this study demonstrated that circRNA may act as a significant diagnostic and prognostic biomarker for pancreatic cancer.

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Prognostic and diagnostic significance of circRNAs expression in hepatocellular carcinoma patients: A meta-analysis.

Publications

Prognostic and diagnostic significance of circRNAs expression in hepatocellular carcinoma patients: A meta-analysis.

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