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

细胞淋巴瘤 2/microRNA-497 基因表达比率评分与结直肠癌患者转移的关联:倾向匹配队列分析

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作者:Shahad W Kattan, Yahya H Hobani, Nouf Abubakr Babteen, Saleh A Alghamdi, Eman A Toraih, Afaf T Ibrahiem, Manal S Fawzy, Salwa Faisal

Background

Deregulated 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.

Conclusion

The BCL2/miR497 expression ratio is associated with poor CRC prognosis in terms of metastasis and short survival.

Methods

Archived 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.

Purpose

To investigate the BCL2/miRNA-497 expression ratio in colorectal cancer (CRC) and explore its association with the clinicopathological characteristics and CRC prognosis.

Results

B-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.

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