Hepatocellular carcinoma associated microRNA expression signature: integrated bioinformatics analysis, experimental validation and clinical significance

摘要: // Ke-Qing Shi 1 , Zhuo Lin Xiang-Jian Chen 2 Mei Song Yu-Qun Wang Yi-Jing Cai Nai-Bing Yang Ming-Hua Zheng Jin-Zhong Dong Lei Zhang Yong-Ping Department of Infection and Liver Diseases, Research Center, The First Affiliated Hospital Wenzhou Medical University, 325000, Zhejiang Province, China General Surgery, Correspondence to: Chen, e-mail: ypchen1959@163.com Keywords: hepatocellular carcinoma, microRNA, biomarker, signature, robust rank aggregation Received: April 09, 2015      Accepted: June 19, Published: 30, 2015 ABSTRACT microRNA (miRNA) expression profiles varied greatly among current studies due to different technological platforms small sample size. Systematic integrative analysis published datesets that compared the miRNA between carcinoma (HCC) tissue paired adjacent noncancerous liver was performed determine candidate HCC associated miRNAs. Moreover, we further validated confirmed miRNAs in a clinical setting using qRT-PCR Tumor Cancer Genome Atlas (TCGA) dataset. A integrated-signature 5 upregulated 8 downregulated identified from 26 method. demonstrated miR-93-5p, miR-224-5p, miR-221-3p miR-21-5p increased, whereas miR-214-3p, miR-199a-3p, miR-195-5p, miR-150-5p miR-145-5p decreased tissues, which also on TCGA based score LASSO regression model provided high accuracy for identifying (AUC = 0.982): risk 0.180E_miR-221 + 0.0262E_miR-21 - 0.007E_miR-223 0.185E_miR-130a. E_miR-n Log (expression n). Furthermore, (miR-222, miR-221, miR-21 miR-214 miR-130a) correlated with pathological tumor grade. Cox showed related 3-year survival (hazard ratio [HR]: 1.509, 95%CI: 1.079–2.112, P 0.016) 5-year (HR: 1.416, 1.057–1.897, 0.020). However, none deregulated microscopic vascular invasion. This study provides basis application HCC.