微小RNA-146a作为食管鳞状细胞癌的预后生物标志物
MicroRNA-146a as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma.
作者信息
Sadegh Shesh Poli Maryam, Khajeniazi Safoura, Behnampour Nasser, Kalani Mohammad Reza, Moradi Abdolvahab, Marjani Abdoljalal
机构信息
School of New Technologies, Golestan University of Medical Sciences, Gorgan, Iran.
Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
出版信息
Cancer Manag Res. 2020 Feb 11;12:973-980. doi: 10.2147/CMAR.S229397. eCollection 2020.
BACKGROUND AND AIMS
MicroRNAs including miR146a have a regulatory role on the expression of genes and act with binding to 3'-UTR region of the genes. Cyclooxygenase-2 (COX-2) is involved in carcinogenesis as an inflammatory marker, and microRNA-146a (miR-146a) as a negative regulatory factor. We aimed to evaluate miR146a expression as a prognostic or diagnostic biomarker for esophageal squamous cell carcinoma (ESCC) and also an association between miR146a and COX2 expression.
MATERIALS AND METHODS
We quantified the level of miR-146a and COX-2 expression in cancerous and adjacent normal tissue samples obtained from 34 patients with ESCC, using real-time-PCR. Statistical analyses were conducted using one-sample -test. Receiver-operating characteristic (ROC) curve and Kaplan-Meier analysis were applied to assay miR146a as a diagnostic and prognostic marker, respectively, during 4 years of the study. Furthermore, the Cox regression model was performed to assay the hazard ratio (HR). The association between miR-146a and COX2 expression level in ESCC patients was evaluated by nonparametric Spearman's rho analysis.
RESULTS
The results revealed a reduction of miR-146a expression in 50% of cancerous tissue when compared with adjacent normal regions (value=0.127). COX-2 expression in 80% of ESCC patients was higher than in the controls (value=0.001). Overall, in 60% of cases, direct association was seen between microRNA-146a and COX-2 expression level (correlation coefficient= 0.438, value=0.011). COX2 can be considered as a diagnostic biomarker (AUC=0.834, sensitivity=72%, specificity =83%, -value<0.0001) but miR146a cannot be considered as a diagnostic biomarker (AUC=0.553, sensitivity=88%, specificity =28%, -value=0.453). Survival analysis by Kaplan-Meier method showed miR146a and COX2 expression can be probably considered as prognostic biomarkers for ESCC because patients with high expression of miR146a had 7 months shorter life span and patients with low expression of COX2 had 8 months shorter life span.
CONCLUSION
COX2 expression is a diagnostic biomarker. MiR-146a and COX2 expression can probably be considered as prognostic biomarkers for survival in ESCC.
背景与目的
包括miR146a在内的微小RNA对基因表达具有调控作用，通过与基因的3'-UTR区域结合发挥作用。环氧合酶-2（COX-2）作为一种炎症标志物参与致癌过程，而微小RNA-146a（miR-146a）作为负调控因子。我们旨在评估miR146a作为食管鳞状细胞癌（ESCC）的预后或诊断生物标志物，以及miR146a与COX2表达之间的关联。
材料与方法
我们使用实时定量PCR技术，对34例ESCC患者的癌组织及癌旁正常组织样本中miR-146a和COX-2的表达水平进行了定量分析。采用单样本t检验进行统计学分析。在4年的研究期间，分别应用受试者工作特征（ROC）曲线和Kaplan-Meier分析来检测miR146a作为诊断和预后标志物的情况。此外，采用Cox回归模型检测风险比（HR）。通过非参数Spearman秩相关分析评估ESCC患者中miR-146a与COX2表达水平之间的关联。
结果
结果显示，与癌旁正常区域相比，50%的癌组织中miR-146a表达降低（t值=0.127）。80%的ESCC患者中COX-2表达高于对照组（t值=0.001）。总体而言，在60%的病例中，微小RNA-146a与COX-2表达水平之间存在直接关联（相关系数=0.438，P值=0.011）。COX2可被视为诊断生物标志物（AUC=0.834，敏感性=72%，特异性=83%，P值<0.0001），但miR146a不能被视为诊断生物标志物（AUC=0.553，敏感性=88%，特异性=28%，P值=0.453）。Kaplan-Meier方法进行的生存分析表明，miR146a和COX2表达可能被视为ESCC的预后生物标志物，因为miR146a高表达的患者寿命缩短7个月，COX2低表达的患者寿命缩短8个月。
结论
COX2表达是一种诊断生物标志物。miR-146a和COX2表达可能被视为ESCC生存的预后生物标志物。
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