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Development and validation of a 14-gene signature for prognosis prediction in hepatocellular carcinoma

机译：肝细胞癌预后预测14-基因签名的开发与验证

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Worldwide, hepatocellular carcinoma (HCC) remains a crucial medical problem. Precise and concise prognostic models are urgently needed because of the intricate gene variations among liver cancer cells. We conducted this study to identify a prognostic gene signature with biological significance. We applied two algorithms to generate differentially expressed genes (DEGs) between HCC and normal specimens in The Cancer Genome Atlas cohort (training set included) and performed enrichment analyses to expound on their biological significance. A protein-protein interactions network was established based on the STRING online tool. We then used Cytoscape to screen hub genes in crucial modules. A multigene signature was constructed by Cox regression analysis of hub genes to stratify the prognoses of HCC patients in the training set. The prognostic value of the multigene signature was externally validated in two other sets from Gene Expression Omnibus (GSE14520 and GSE76427), and its role in recurrence prediction was also investigated. A total of 2000 DEGs were obtained, including 1542 upregulated genes and 458 downregulated genes. Subsequently, we constructed a 14-gene signature on the basis of 56 hub genes, which was a good predictor of overall survival. The prognostic signature could be replicated in GSE14520 and GSE76427. Moreover, the 14-gene signature could be applied for recurrence prediction in the training set and GSE14520. In summary, the 14-gene signature extracted from hub genes was involved in some of the HCC-related signalling pathways; it not only served as a predictive signature for HCC outcome but could also be used to predict HCC recurrence.
机译：全球性肝细胞癌（HCC）仍然是至关重要的医学问题。由于肝癌细胞中复杂的基因变异，迫切需要精确而简洁的预后模型。我们进行了该研究以鉴定具有生物学意义的预后基因签名。我们应用两种算法在癌症基因组地图集队列（包括训练集）中产生HCC和常规样本之间的差异表达基因（DEG），并进行了富集分析以阐述其生物意义。基于字符串在线工具建立蛋白质 - 蛋白质相互作用网络。然后，我们使用Cytoscape在关键模块中筛选枢纽基因。通过枢纽基因的Cox回归分析构建多烯签名，以分析训练集中HCC患者的预期。多烯签名的预后值在来自基因表达Omnibus（GSE14520和GSE76427）的另外两组中外部验证，并研究了其在复发预测中的作用。获得共有2000次，其中包括1542个上调基因和458个下调基因。随后，我们在56个枢纽基因中构建了14个基因签名，这是整体存活的良好预测因子。可以在GSE14520和GSE76427中复制预后签名。此外，可以应用14-基因签名在训练集和GSE14520中的复发预测。总之，从集线器基因提取的14-基因签名参与其中一些与HCC相关的信号通路;它不仅担任HCC结果的预测签名，而且还可用于预测HCC复发。

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