Tang Yunliang, Zeng Zhenguo, Wang Jiao, Li Guoyong, Huang Chao, Dong Xiaoyang, Feng Zhen
Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University Nanchang, Jiangxi, People's Republic of China.
Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University Nanchang, Jiangxi, People's Republic of China.
Am J Transl Res. 2020 Apr 15;12(4):1184-1202. eCollection 2020.
Hepatocellular carcinoma (HCC) is one of the most common internal malignancies worldwide and is associated with a poor prognosis. There is an urgent need to identify diagnostic and prognostic biomarkers of HCC pathogenesis and progression. Accordingly, in this study, we analyzed differentially expressed immune-related genes (IRGs) from 329 patients with HCC from The Cancer Genome Atlas datasets. Functional analysis revealed that the IRGs had potential effects on tumor immune processes, such as inflammatory responses and growth factor activity. In the training group, we constructed a nine-IRG formula to predict prognosis in patients with HCC. To validate the protein and mRNA levels of these IRGs, we used the Human Protein Atlas database and quantitative PCR analysis and found that most protein expression levels matched the corresponding mRNA expression levels. Furthermore, we also validated the prognostic value of the new risk model in another independent cohort (n = 277) from a Gene Expression Omnibus dataset (GSE14520). Our data suggested that there was a significant association between our risk model and patient prognosis. Stratification analysis showed that the nine-IRG signature was significantly associated with overall survival in men. Finally, the signature was found to be correlated with various clinicopathological features. Intriguingly, the prognostic index based on the IRGs reflected infiltration by several types of immune cells. In summary, our data provided evidence that the nine-IRG signature could serve as an independent biomarker to predict prognosis in patients with HCC.
肝细胞癌(HCC)是全球最常见的内部恶性肿瘤之一,且预后较差。迫切需要确定HCC发病机制和进展的诊断及预后生物标志物。因此,在本研究中,我们分析了来自癌症基因组图谱数据集的329例HCC患者的差异表达免疫相关基因(IRG)。功能分析表明,这些IRG对肿瘤免疫过程具有潜在影响,如炎症反应和生长因子活性。在训练组中,我们构建了一个九基因IRG公式来预测HCC患者的预后。为了验证这些IRG的蛋白质和mRNA水平,我们使用了人类蛋白质图谱数据库和定量PCR分析,发现大多数蛋白质表达水平与相应的mRNA表达水平相匹配。此外,我们还在另一个来自基因表达综合数据库(GSE14520)的独立队列(n = 277)中验证了新风险模型的预后价值。我们的数据表明,我们的风险模型与患者预后之间存在显著关联。分层分析显示,九基因IRG特征与男性患者的总生存期显著相关。最后,发现该特征与各种临床病理特征相关。有趣的是,基于IRG的预后指数反映了几种免疫细胞的浸润情况。总之,我们的数据提供了证据,表明九基因IRG特征可作为预测HCC患者预后的独立生物标志物。