Association of B-cell lymphoma 2/microRNA-497 gene expression ratio score with metastasis in patients with colorectal cancer: A propensity-matched cohort analysis.

Abstract

BackgroundDeregulated microRNAs (miRs) significantly impact cancer development and progression. Our in silico analysis revealed that miR‐497 and its target gene B‐cell lymphoma‐2 (BCL2) could be related to poor cancer outcomes.PurposeTo investigate the BCL2/miRNA‐497 expression ratio in colorectal cancer (CRC) and explore its association with the clinicopathological characteristics and CRC prognosis.MethodsArchived samples from 106 CRC patients were enrolled. MiR‐497 and BCL2 gene expressions were detected by Taq‐Man Real‐Time quantitative polymerase chain reaction in propensity‐matched metastatic and nonmetastatic cohorts after elimination of confounder bias.ResultsB‐cell lymphoma‐2 gene was upregulated in metastatic samples (median = 1.16, 95%CI = 1.09–1.60) compared to nonmetastatic (median = 1.02, 95%CI = 0.89–1.25, p < 0.001). In contrast, lower levels of miR‐495 were detected in specimens with distant metastasis (median = 0.05, 95%CI = 0.04–0.20) than nonmetastatic samples (median = 0.54, 95%CI = 0.47–0.58, p < 0.001). Estimated BCL2/miR‐497 ratio yielded a significant differential expression between the two cohort groups. Higher scores were observed in metastasis group (median = 1.39, 95%CI = 0.9–1.51) than nonmetastatic patients (median = 0.29, 95%CI = 0.19–0.39, p < 0.001). Receiver operating characteristic curve analysis showed BCL2/miR‐497 ratio score to have the highest predictive accuracy for metastasis at presentation. The area under the curve was 0.90 (95%CI = 0.839–0.964, p < 0.001) at cut‐off of >0.525, with high sensitivity 81.1% (95%CI = 68.6%–89.4%) and specificity 92.5% (95%CI = 82.1%–97.0%). Also, the ratio score was negatively correlated with disease‐free survival (r = −0.676, p < 0.001) and overall survival times (r = −0.650, p < 0.001). Kaplan–Meier curves showed lower survival rates in cohorts with high‐score compared to low‐score patients.ConclusionThe BCL2/miR497 expression ratio is associated with poor CRC prognosis in terms of metastasis and short survival.