Application of microRNA and mRNA expression profiling on prognostic biomarker discovery for hepatocellular carcinoma

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• 作者：Lin Wei (41) (42)
  Baofeng Lian (43) (44)
  Yuannv Zhang (42)
  Wei Li (43)
  Jianren Gu (42)
  Xianghuo He (42)
  Lu Xie (43)
  
• 关键词：Hepatocellular Carcinoma ; Gene Expression Profile ; Gene Set Enrichment Analysis ; Prognosis ; microRNA
• 刊名：BMC Genomics
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：15
• 期：1-supp
• 全文大小：1,682 KB
• 作者单位：Lin Wei (41) (42)
  Baofeng Lian (43) (44)
  Yuannv Zhang (42)
  Wei Li (43)
  Jianren Gu (42)
  Xianghuo He (42)
  Lu Xie (43)
  
  41. Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China
  42. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, P. R. China
  43. Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai, 201203, P. R. China
  44. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China
  
• ISSN：1471-2164

文摘

Background Hepatocellular carcinoma (HCC) is one of the most highly malignant and lethal cancers of the world. Its pathogenesis has been reported to be multi-factorial, and the molecular carcinogenesis of HCC can not be attributed to just a few individual genes. Based on the microRNA and mRNA expression profiling of normal liver tissues, pericancerous hepatocellular tissues and hepatocellular carcinoma tissues, we attempted to find prognosis related gene sets for HCC patients. Results We identified differentially expressed genes (DEG) from three comparisons: Cancer/Normal, Cancer/Pericancerous and Pericancerous/Normal. GSEA (gene set enrichment analysis) were performed. Based on the enriched gene sets of GO terms, pathways and transcription factor targets, it was found that the genome instability and cell proliferation increased while the metabolism and differentiation decreased in HCC tissues. The expression profile of DEGs in each enriched gene set was used to correlate to the postoperative survival time of HCC patients. Nine gene sets were found to prognostic correlation. Furthermore, after substituting DEG-targeting-microRNA for DEG members of each gene set, two gene sets with the microRNA expression profiles were obtained that had prognostic potential. Conclusions The malignancy of HCC could be represented by gene sets, and pericancerous liver exhibits important characteristics of liver cancer. The expression level of gene sets not only in HCC but also in the pericancerous liver showed potential for prognosis implying an option for HCC prognosis at an early stage. Additionally, the gene-targeting-microRNA expression profiles also showed prognostic potential, demonstrating that the multi-factorial molecular pathogenesis of HCC is contributed by various genes and microRNAs.