Identification and functional analysis of differentially expressed genes in poorly differentiated hepatocellular carcinoma using RNA-seq

// Yi Huang 1, 2, * , Jianbo Pan 3, * , Dunyan Chen 1, 2 , Jiaying Zheng 1, 2 , Funan Qiu 1, 4 , Feng Li 2, 5 , Yanan Wu 1, 2 , Wenbing Wu 1, 2 , Xiaoli Huang 1, 2 , Jiang Qian 3, 6 1 Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China 2 Provincial Clinical College, Fujian Medical University, Fuzhou, Fujian 350001, China 3 Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA 4 Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China 5 Department of Pathology, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China 6 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA * These authors contributed equally to this work Correspondence to: Yi Huang, email: hyi1971@126.com Jiang Qian, email: jiang.qian@jhmi.edu Keywords: hepatocellular carcinoma, poorly differentiated, transcriptome sequencing, differentially expressed genes, carcinogenesis Received: February 07, 2017      Accepted: March 12, 2017      Published: March 21, 2017 ABSTRACT Poorly differentiated (PD) hepatocellular carcinoma (HCC) has a worse prognosis compared to moderately differentiated (MD) and well differentiated (WD) HCC. We aimed to identify differentially expressed genes (DEGs) to explore the mechanism of PD HCC. Transcriptome sequencing was performed on tumor and adjacent non-tumorous tissues of PD, MD and WD HCC patients (3 for each group). DEGs were thus identified and functionally analyzed. Further RT-PCR was performed to validate DEGs specific for PD HCC in 47 pairs of samples (15 for PD, 18 for MD, 14 for WD). A total of 681 PD DEGs were detected, including 368 up-regulated and 313 down-regulated genes. Less DEGs were found for MD and especially for WD HCC. Through bioinformatics analysis, PD HCC DEGs were enriched in liver tissue and liver cancer cells, and in biological process and pathway including metabolism, cell cycle, translation and blood coagulation. Potential drugs and genetic perturbations were found to reverse the cancer condition. The RT-PCR results showed consistency with RNA-seq in the validation of 4 DEGs specific for PD HCC. This study detected and validated DEGs of PD HCC, which provides useful information on molecular mechanism of PD HCC for development of new biomarkers, therapeutic targets and drugs.