B 细胞淋巴瘤 2/微小 RNA-497 基因表达比值评分与结直肠癌患者转移的相关性：倾向评分匹配队列分析。

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

机构信息

Department of Medical Laboratory, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia.

Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia.

出版信息

J Clin Lab Anal. 2022 Feb;36(2):e24227. doi: 10.1002/jcla.24227. Epub 2022 Jan 7.

DOI:10.1002/jcla.24227

PMID:34994989

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8841134/

Abstract

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.

PURPOSE

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

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.

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.

CONCLUSION

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

摘要

背景

失调的 microRNAs（miRs）显著影响癌症的发生和发展。我们的计算机分析显示，miR-497及其靶基因 B 细胞淋巴瘤-2（BCL2）可能与不良的癌症预后有关。

目的

研究结直肠癌（CRC）中 BCL2/miRNA-497 表达比率，并探讨其与临床病理特征和 CRC 预后的关系。

方法

纳入 106 例 CRC 患者的存档样本。在排除混杂因素的偏倚后，采用 Taq-Man 实时定量聚合酶链反应检测转移性和非转移性亚组中 miR-497 和 BCL2 基因的表达。

结果

与非转移性样本（中位数=1.02，95%CI=0.89-1.25，p<0.001）相比，转移性样本中 B 细胞淋巴瘤-2 基因表达上调（中位数=1.16，95%CI=1.09-1.60）。相反，远处转移标本中 miR-495 水平较低（中位数=0.05，95%CI=0.04-0.20），而非转移性标本中 miR-495 水平较高（中位数=0.54，95%CI=0.47-0.58，p<0.001）。估计的 BCL2/miR-497 比值在两个队列组之间有显著的差异表达。转移组的评分较高（中位数=1.39，95%CI=0.9-1.51），而非转移性患者的评分较低（中位数=0.29，95%CI=0.19-0.39，p<0.001）。受试者工作特征曲线分析显示，BCL2/miR-497 比值评分对首发转移具有最高的预测准确性。曲线下面积为 0.90（95%CI=0.839-0.964，p<0.001），截断值>0.525，敏感性为 81.1%（95%CI=68.6%-89.4%），特异性为 92.5%（95%CI=82.1%-97.0%）。此外，比值评分与无病生存率（r=-0.676，p<0.001）和总生存时间（r=-0.650，p<0.001）呈负相关。Kaplan-Meier 曲线显示，高评分组的生存率低于低评分组。