Chen XiangJian, Shi KeQing, Wang YuQun, Song Mei, Zhou Wu, Tu HongXiang, Lin Zhuo
Department of Endoscopic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Oncotarget. 2015 Nov 10;6(35):37544-56. doi: 10.18632/oncotarget.6065.
MicroRNA (miRNA) expression profiling of colorectal cancer (CRC) are often inconsistent among different studies. To determine candidate miRNA biomarkers for CRC, we performed an integrative analysis of miRNA expression profiling compared CRC tissues and paired neighboring noncancerous colorectal tissues. Using robust rank aggregation method, we identified a miRNA set of 10 integrated-signature miRNAs. In addition, the qRT-PCR validation demonstrated that 9 miRNAs were consistent dysregulated with the integrative analysis in CRC tissues, 4 miRNAs (miR-21-5p, miR-183-5p, miR-17-5p and miR-20a-5p) were up-regulated expression, and 5 miRNAs (miR-145-5p, miR-195-5p, miR-139-5p, miR-378a-5p and miR-143-3p) were down-regulated expression (all p < 0.05). Consistent with the initial analysis, 7 miRNAs were found to be significantly dysregulated in CRC tissues in TCGA data base, 4 miRNAs (miR-21-5p, miR-183-5p, miR-17-5p and miR-20a-5p) were significantly up-regulated expression, and 3 miRNAs (miR-145-5p, miR-139-5p and miR-378a-5p) were significantly down-regulated expression in CRC tissues (all p < 0.001). Furthermore, miR-17-5p (p = 0.011) and miR-20a-5p (p = 0.003) were up-regulated expression in the III/IV tumor stage, miR-145-5p (p = 0.028) and miR-195-5p (p = 0.001) were significantly increased expression with microscopic vascular invasion in CRC tissues, miR-17-5p (p = 0.037) and miR-145-5p (p = 0.023) were significantly increased expression with lymphovascular invasion. Moreover, Cox regression analysis of CRC patients in TCGA data base showed miR-20a-5p was correlated with survival (hazard ratio: 1.875, 95%CI: 1.088-3.232, p = 0.024). Hence, the finding of current study provides a basic implication of these miRNAs for further clinical application in CRC.
不同研究中,结直肠癌(CRC)的微小RNA(miRNA)表达谱往往不一致。为了确定CRC的候选miRNA生物标志物,我们对miRNA表达谱进行了综合分析,比较了CRC组织和配对的相邻非癌性结直肠组织。使用稳健秩聚合方法,我们鉴定出一组由10个整合特征miRNA组成的miRNA集。此外,qRT-PCR验证表明,9个miRNA在CRC组织中的失调与综合分析结果一致,4个miRNA(miR-21-5p、miR-183-5p、miR-17-5p和miR-20a-5p)表达上调,5个miRNA(miR-145-5p、miR-195-5p、miR-139-5p、miR-378a-5p和miR-143-3p)表达下调(所有p<0.05)。与初始分析一致,在TCGA数据库中发现7个miRNA在CRC组织中显著失调,4个miRNA(miR-21-5p、miR-183-5p、miR-17-5p和miR-20a-5p)在CRC组织中显著上调表达,3个miRNA(miR-145-5p、miR-139-5p和miR-378a-5p)在CRC组织中显著下调表达(所有p<0.001)。此外,miR-17-5p(p = 0.011)和miR-20a-5p(p = 0.003)在III/IV期肿瘤中表达上调,miR-145-5p(p = 0.028)和miR-195-5p(p = 0.001)在CRC组织中随微血管侵犯显著增加表达,miR-17-5p(p = 0.037)和miR-145-5p(p = 0.023)随淋巴管侵犯显著增加表达。此外,对TCGA数据库中CRC患者的Cox回归分析显示,miR-20a-5p与生存相关(风险比:1.875,95%CI:1.088 - 3.232,p = 0.024)。因此,本研究结果为这些miRNA在CRC中的进一步临床应用提供了基本启示。
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