TMEM88, CCL14 and CLEC3B as prognostic biomarkers for prognosis and palindromia of human hepatocellular carcinoma
TMEM88, CCL14 and CLEC3B as prognostic biomarkers for prognosis and palindromia of human hepatocellular carcinoma
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TMEM88、CCL14 和 CLEC3B 作为人肝细胞癌预后和回文的预后生物标志物
DOI：
10.1177/1010428317708900
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发表时间：
2017-07-18
期刊：
影响因子：
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通讯作者：
Liu, Jia-Qiang
中科院分区：
文献类型：
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作者：
Zhang, Xin;Wan, Jin-Xiang;Liu, Jia-Qiang
肝细胞癌是世界范围内发病率不断上升的最常见的恶性肿瘤之一。阐明肝细胞癌预后和回文的遗传驱动基因有助于管理患者的临床决策。本研究利用IlluminaHiSeq平台从The Cancer Genome Atlas下载了330例原发性肝细胞癌患者样本的高通量RNA测序数据。确定差异表达的稳定关键基因，使用R语言的考克斯比例风险检验进行Kaplan-Meier生存分析。采用聚类分析确定影响该病预后的驱动基因。通过文献检索和基因集富集分析进行驱动基因的功能分析。最后，使用外部数据集GSE 40873验证所选择的驱动基因。共筛选出5781个稳定的关键基因，其中156个基因与肝癌发生密切相关。根据重要的关键基因，将样本分为五个聚类，并根据临床特征进一步整合为高风险和低风险类别。选择TMEM 88、CCL 14和CLEC 3B作为驱动基因，其成功地聚集了高/低风险患者（通常，p = 0.0005124445）。最后，来自外部数据库的高/低风险样本的生存分析显示了显著差异，p值0.0198。TMEM 88、CCL 14和CLEC 3B基因在预测肝癌患者的生存期和复发时间方面是稳定的。这些基因可以作为潜在的预后基因，有助于改善患者的预后和生存。
Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan–Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients’ outcomes and survival.