Research Papers:

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

Ke-Qing Shi _, Zhuo Lin, Xiang-Jian Chen, Mei Song, Yu-Qun Wang, Yi-Jing Cai, Nai-Bing Yang, Ming-Hua Zheng, Jin-Zhong Dong, Lei Zhang and Yong-Ping Chen

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Oncotarget. 2015; 6:25093-25108. https://doi.org/10.18632/oncotarget.4437

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Ke-Qing Shi1, Zhuo Lin1, Xiang-Jian Chen2, Mei Song1, Yu-Qun Wang1, Yi-Jing Cai1, Nai-Bing Yang1, Ming-Hua Zheng1, Jin-Zhong Dong1, Lei Zhang1, Yong-Ping Chen1

1Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China

2Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China

Correspondence to:

Yong-Ping Chen, e-mail: [email protected]

Keywords: hepatocellular carcinoma, microRNA, biomarker, signature, robust rank aggregation

Received: April 09, 2015     Accepted: June 19, 2015     Published: June 30, 2015


microRNA (miRNA) expression profiles varied greatly among current studies due to different technological platforms and small sample size. Systematic and integrative analysis of published datesets that compared the miRNA expression profiles between hepatocellular carcinoma (HCC) tissue and paired adjacent noncancerous liver tissue was performed to determine candidate HCC associated miRNAs. Moreover, we further validated the confirmed miRNAs in a clinical setting using qRT-PCR and Tumor Cancer Genome Atlas (TCGA) dataset. A miRNA integrated-signature of 5 upregulated and 8 downregulated miRNAs was identified from 26 published datesets in HCC using robust rank aggregation method. qRT-PCR demonstrated that miR-93-5p, miR-224-5p, miR-221-3p and miR-21-5p was increased, whereas the expression of miR-214-3p, miR-199a-3p, miR-195-5p, miR-150-5p and miR-145-5p was decreased in the HCC tissues, which was also validated on TCGA dataset. A miRNA based score using LASSO regression model provided a high accuracy for identifying HCC tissue (AUC = 0.982): HCC risk score = 0.180E_miR-221 + 0.0262E_miR-21 - 0.007E_miR-223 - 0.185E_miR-130a. E_miR-n = Log 2 (expression of microRNA n). Furthermore, expression of 5 miRNAs (miR-222, miR-221, miR-21 miR-214 and miR-130a) correlated with pathological tumor grade. Cox regression analysis showed that miR-21 was related with 3-year survival (hazard ratio [HR]: 1.509, 95%CI: 1.079–2.112, P = 0.016) and 5-year survival (HR: 1.416, 95%CI: 1.057–1.897, P = 0.020). However, none of the deregulated miRNAs was related with microscopic vascular invasion. This study provides a basis for further clinical application of miRNAs in HCC.

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