BMC Genomics. 2014;15 Suppl 1(Suppl 1):S13. doi: 10.1186/1471-2164-15-S1-S13. Epub 2014 Jan 24.
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.
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.
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.
肝细胞癌（HCC）是世界上最恶性和致命的癌症之一。其发病机制被报道为多因素的，HCC 的分子癌变不能仅仅归因于少数几个个体基因。基于正常肝组织、癌旁肝细胞组织和肝癌组织的 microRNA 和 mRNA 表达谱，我们试图为 HCC 患者找到与预后相关的基因集。
我们从三个比较中鉴定出差异表达基因（DEG）：Cancer/Normal、Cancer/Pericancerous 和 Pericancerous/Normal。进行了 GSEA（基因集富集分析）。基于 GO 术语、途径和转录因子靶标的富集基因集，发现 HCC 组织中的基因组不稳定性和细胞增殖增加，而代谢和分化减少。每个富集基因集中 DEG 的表达谱用于与 HCC 患者的术后生存时间相关联。发现九个基因集与预后相关。此外，在用 DEG 靶向 microRNA 替代每个基因集中的 DEG 成员后，获得了两个具有潜在预后的 microRNA 表达谱的基因集。
HCC 的恶性程度可以用基因集来表示，癌旁肝表现出肝癌的重要特征。基因集的表达水平不仅在 HCC 中，而且在癌旁肝中都显示出预后的潜力，这为 HCC 的早期预后提供了一种选择。此外，基因靶向 microRNA 的表达谱也显示出预后潜力，表明 HCC 的多因素分子发病机制是由各种基因和 microRNA 共同作用的。
