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Prediction of poor prognosis in breast cancer patients based on microRNA-21 expression: a meta-analysis.

ABSTRACT: MicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer.The meta-analysis was conducted by searching the databases of PubMed, EMBASE, Web of Science and Chinese database-China National Knowledge Infrastructure (CNKI). Data were extracted from studies that investigated the association between miR-21 expression and survival outcomes in breast cancer patients. With respect to survival outcomes, the pooled hazard ratios (HRs) of miR-21 were calculated given a 95% confidence interval (CI).Our meta-analysis identified a total of 10 studies involving 1,439 cases. Further investigation demonstrated that a high miR-21 expression can predict poor overall survival (OS) (HR = 2.57, 95% CI: 1.37-4.81, P = 0.003) and shortened disease-free/recurrence-free survival (DFS/RFS) (HR = 1.45, 95% CI: 1.16-1.82, P = 0.001) in breast cancer patients. Moreover, high miR-21 expression was significantly correlated with lowered OS in the Asian group (HR = 5.07, 95% CI: 2.89-8.92, P < 0.001), but not in the Caucasian cohort (HR = 1.44, 95% CI: 0.99-2.10, P = 0.058). Furthermore, odds ratios (ORs) showed that up-regulated miR-21 levels were associated with multiple clinical characteristics.Our results indicated that miR-21 can predict unfavorable prognoses in breast cancer patients, especially in Asians.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4338069 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Prediction of poor prognosis in breast cancer patients based on microRNA-21 expression: a meta-analysis.

Wang Yanyan Y Zhang Yujie Y Pan Chi C Ma Feixia F Zhang Suzhan S

PloS one 20150223 2

<h4>Background</h4>MicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer.<h4>Methods</h4>The meta-analysis was conducted by searching the databases of PubMed, EMBASE, Web of Science and Chinese database-China National Knowledge Infrastructure (CNKI). Data were extracted from studies that investigate ...[more]

PMID: 25706383

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Project description:Although keratin 15 (KRT15) has been indicated to be overexpressed in several types of tumor, its role in breast invasive carcinoma (BRCA) has so far remained elusive. The aim of the present study was to explore KRT15 expression in BRCA based on data obtained from The Cancer Genome Atlas and The Genotype-Tissue Expression. KRT15 expression was compared using a Wilcoxon rank-sum test. Functional enrichment analysis was performed to reveal the biological roles and pathways of KRT15. The association between KRT15 expression and immune-cell infiltration was evaluated via single-sample gene set enrichment analysis (ssGSEA). To investigate the relationship between clinicopathological features and KRT15 expression, the prognostic value of KRT15 and other clinical factors was evaluated using Cox regression analysis and Kaplan-Meier (KM) plots. Subgroup prognostic analysis was also performed using forest plots and KM curves. Finally, a tissue microarray was used to assess KRT15 expression in BRCA tissues. KRT15 expression was significantly lower in BRCA tissues compared with that in normal tissues. Functional enrichment analysis suggested that KRT15-related genes were primarily enriched in the transmembrane transporter complex, cornification and ligand-receptor interactions. Increased KRT15 was associated with several tumor-suppressive pathways. ssGSEA revealed that high KRT15 expression was significantly associated with natural killer-cell, B-cell and mast-cell infiltration. Significant associations were observed between low KRT15 expression and advanced stage clinicopathological factors, as well as unfavorable overall survival (OS) and disease-specific survival. Multivariate Cox regression analysis suggested that KRT15 was an independent prognostic factor for OS (P=0.039; hazard ratio, 0.590; 95% CI, 0.358-0.974). Subgroup prognostic analysis demonstrated that low KRT15 was a reliable predictor of poor OS. Immunohistochemistry of a tissue microarray indicated that positive KRT15 expression rates were significantly higher in normal tissues compared with those in the BRCA tissues. In conclusion, low KRT15 expression was significantly associated with poor prognosis in patients with BRCA. Thus, KRT15 may serve an important role in BRCA progression and may be used as a promising prognostic marker for diagnostic and prognostic analyses in patients with BRCA.

Project description:BackgroundRECQL is a number of the RecQ DNA helicase family and plays an important role in maintaining genome stability. Although several studies have reported that RECQL mutations were correlated with the susceptibility to breast cancer, the effect on prognosis in breast cancer was not yet clarified. Here, we explored the association between RECQL expression level and survival in patients with breast cancer.MethodsIn the first cohort, the RECQL mRNA expression level was evaluated in 774 primary breast cancer patients using a quantitative real-time PCR assay. Then, in the second independent cohort, the level of RECQL protein expression was detected in 322 patients with breast cancer using immunohistochemistry assay. Survival curves of patients with RECQL expression were compared using the Kaplan-Meier method with log-rank test.ResultsIn the first cohort of 774 breast cancer patients, the low expression level of RECQL mRNA was significantly correlated with aggressive clinicopathological characteristics, including the positive lymph node status (P = 0.026), HER2 overexpression (P < 0.001), ER negative status (P = 0.047) and high tumor grade (P = 0.041). Moreover, the low expression level of RECQL mRNA was significantly associated with poor distant recurrence-free survival (DRFS, unadjusted hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.88-4.09, P < 0.001) and disease-specific survival (DSS, unadjusted HR: 3.10, 95% CI: 1.84-5.20,P < 0.001), and it remained an independent unfavorable factor for DRFS and DSS (DRFS: adjusted HR: 3.04, 95% CI: 1.89-4.87, P < 0.001; DSS: adjusted HR: 4.25, 95% CI: 2.12-8.46, P < 0.001). In the second cohort of 322 breast cancer patients, low expression of RECQL protein was also subject to poor survival in breast cancer, and it was an independent prognosis factor of poor DRFS by multivariate analysis (DRFS: adjusted HR: 2.12, 95% CI: 1.16-3.88, P = 0.015).ConclusionsBreast cancer patients with low RECQL expression had a worse survival. The expression level of RECQL may be a potential prognosis factor for breast cancer.

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Prediction of poor prognosis in breast cancer patients based on microRNA-21 expression: a meta-analysis.

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Prediction of poor prognosis in breast cancer patients based on microRNA-21 expression: a meta-analysis.

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