Han Lin, Sun Yanjun, Lu Cansheng, Ma Chungeng, Shi Jian, Sun Dengqun
Graduate School, Anhui University of Traditional Chinese Medicine, Hefei, China.
Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China.
Front Genet. 2021 May 28;12:666833. doi: 10.3389/fgene.2021.666833. eCollection 2021.
MiR-3614-5p has been found in a variety of cancers including colorectal cancer. However, the association of miR-3614-5p with colorectal cancer is still unclear. Based on the Cancer Genome Atlas (TCGA) database, the relationship between miR-3614-5p and colorectal cancer can be proved. Wilcoxon rank-sum test was used to compare the miR-3614-5p expression in colorectal cancer tissues and under normal conditions, respectively. The logistic regression method was further employed to analyze the relationship between miR-3614-5p and clinicopathological characteristics. Also, the correlation between miR-3614-5p and survival rate was evaluated by Kaplan-Meier and Cox regression analysis. Besides, gene set enrichment analysis (GSEA) was used to investigate the biological functions of miR-3614-5p. The decrease of miR-3614-5p expression of colorectal cancer was significantly correlated with N stage (OR) = 0.7 for N1&N2 vs. N0), M stage (OR = 0.5 for M1 vs. M0), pathologic stage (OR = 0.7 for Stage III & Stage IV vs. Stage I & Stage II), neoplasm type (OR = 0.5 for rectum adenocarcinoma vs. colon adenocarcinoma), and lymphatic invasion (OR = 0.6 for YES vs. NO) (all -values < 0.05). Kaplan-Meier survival analysis showed that colorectal cancer with low miR-3614-5p has a poorer prognosis than that of high miR-3614-5p ( = 0.005). According to univariate analysis, low miR-3614-5p was associated with poor overall survival (OS) [hazard ratio (HR) = 0.599; 95% confidence interval (CI): 0.418-0.857; = 0.005]. In multivariate analysis, miR-3614-5p was closely related to OS (HR = 0.630; 95% CI: 0.405-0.978, = 0.021). GSEA showed that the high expression phenotype of miR-3614-5p differentially enriches the P53 pathway. Meanwhile, the high expression phenotype of miR-3614-5p enhanced NK T cell activation, negative T cell selection, response to interleukin 2, and response to tumor cells. MiR-3614-5p is a possible prognostic marker of low survival rate for patients with colorectal cancer. Moreover, the P53 pathway and P38MAPK pathway may be the key pathways regulated by miR-3614-5p in colorectal cancer.
已在包括结直肠癌在内的多种癌症中发现了miR-3614-5p。然而,miR-3614-5p与结直肠癌之间的关联仍不清楚。基于癌症基因组图谱(TCGA)数据库,可以证明miR-3614-5p与结直肠癌之间的关系。采用Wilcoxon秩和检验分别比较结直肠癌组织和正常条件下miR-3614-5p的表达。进一步采用逻辑回归方法分析miR-3614-5p与临床病理特征之间的关系。此外,通过Kaplan-Meier和Cox回归分析评估miR-3614-5p与生存率之间的相关性。此外,基因集富集分析(GSEA)用于研究miR-3614-5p的生物学功能。结直肠癌中miR-3614-5p表达的降低与N分期(N1&N2与N0相比,OR = 0.7)、M分期(M1与M0相比,OR = 0.5)、病理分期(III期和IV期与I期和II期相比,OR = 0.7)、肿瘤类型(直肠腺癌与结肠腺癌相比,OR = 0.5)以及淋巴浸润(是与否相比,OR = 0.6)显著相关(所有P值<0.05)。Kaplan-Meier生存分析表明,miR-3614-5p低表达的结直肠癌患者预后比miR-3614-5p高表达的患者差(P = 0.005)。单因素分析显示,miR-3614-5p低表达与总体生存率(OS)差相关[风险比(HR)= 0.599;95%置信区间(CI):0.418 - 0.857;P = 0.005]。多因素分析显示,miR-3614-5p与OS密切相关(HR = 0.630;95%CI:0.405 - 0.978,P = 0.021)。GSEA显示,miR-3614-5p的高表达表型差异富集P53通路。同时,miR-3614-5p的高表达表型增强了NK T细胞活化、阴性T细胞选择、对白介素2的反应以及对肿瘤细胞的反应。miR-3614-5p可能是结直肠癌患者低生存率的预后标志物。此外,P53通路和P38MAPK通路可能是miR-3614-5p在结直肠癌中调控的关键通路。