G2/M checkpoint plays a vital role at the early stage of HCC by analysis of key pathways and genes

// Li Yin 1, 2, 3 , Cuifang Chang 2 and Cunshuan Xu 1, 2 1 College of Life Science, Henan Normal University, Xinxiang 453007, Henan Province, China 2 State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Bioengineering Key Laboratory, Henan Normal University, Xinxiang 453007, Henan Province, China 3 Luohe Medical College, Luohe 462002, Henan Province, China Correspondence to: Cunshuan Xu, email: cellkeylab@126.com Keywords: early HCC, G2/M checkpoint, leading edge analysis, IPA, GSEA Received: February 09, 2017     Accepted: June 29, 2017     Published: July 18, 2017 ABSTRACT The present study was designed to explore the molecular mechanism at the early stage of hepatocarcinoma (HCC) and identify the candidate genes and pathways changed significantly. We downloaded the gene expression file dataset GSE6764 from GEO, adopted the Robust Multi-array Average (RMA) algorithm to preprocess the raw file. 797 differentially expressed genes (DEGs) were screened out based on the SAM method using R language. Ingenuity Pathway Analysis (IPA) was used to perform canonical pathway analysis in order to calculate the most significantly changed pathways and predict the upstream regulators. In order to confirm the results from the DEGs which based on the individual gene level, the gene set enrichment analysis (GSEA) was done from the gene set level and the leading edge analysis was performed to find out the most appeared genes in several gene sets. The PPI network was built using GeneMANIA and the key genes were calculated using cytoHubba plugin based on cytoscape 3.4.0. We found that the Cell Cycle: G2/M DNA damage checkpoint regulation is the top-ranked pathways at the early stage of HCC by IPA. The high expression of several genes including CCNB1, CDC25B, XPO1, GMPS, KPNA2 and MELK is correlated with high risk, poor prognosis and shorter overall survival time in HCC patients by use of Kaplan-Meier Survival analysis. Taken together, our study showed that the G2/M checkpoint plays a vital role at the early HCC and the genes participate in the process may serve as biomarkers for the diagnosis and prognosis.