The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, People's Republic of China.
Department of Geriatrics, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, People's Republic of China.
Sci Rep. 2023 Nov 21;13(1):20380. doi: 10.1038/s41598-023-47886-z.
This study was designed to evaluate the prognosis and pharmacological therapy sensitivity of epithelial mesenchymal transition-related genes (EMTRGs) that obtained from the EMTome database in hepatocellular carcinoma (HCC) using bioinformatical method. The expression status of EMTRGs were also investigated using the clinical information of HCC patients supported by TCGA database and the ICGC database to establish the TCGA cohort as the training set and the ICGC cohort as the validation set. Analyze the EMTRGs between HCC tissue and liver tissue in the TCGA cohort in the order of univariate COX regression, LASSO regression, and multivariate COX regression, and construct a risk model for EMTRGs. In addition, enrichment pathways, gene mutation status, immune infiltration, and response to drugs were also analyzed in the high-risk and low-risk groups of the TCGA cohort, and the protein expression status of EMTRGs was verified. The results showed a total of 286 differentially expressed EMTRGs in the TCGA cohort, and EZH2, S100A9, TNFRSF11B, SPINK5, and CCL21 were used for modeling. The TCGA cohort was found to have a worse outcome in the high-risk group of HCC patients, and the ICGC cohort confirmed this finding. In addition, EMTRGs risk score was shown to be an independent prognostic factor in both cohorts by univariate and multivariate COX regression. The results of GSEA analysis showed that most of the enriched pathways in the high-risk group were associated with tumor, and the pathways enriched in the low-risk group were mainly associated with metabolism. Patients in various risk groups had varying immunological conditions, and the high-risk group might benefit more from targeted treatments. To sum up, the EMTRGs risk model was developed to forecast the prognosis for HCC patients, and the model might be useful in assisting in the choice of treatment drugs for HCC patients.
本研究旨在通过生物信息学方法评估 EMTome 数据库中获得的上皮间质转化相关基因(EMTRGs)在肝细胞癌(HCC)中的预后和药物治疗敏感性。使用 TCGA 数据库和 ICGC 数据库支持的 HCC 患者的临床信息,研究 EMTRGs 的表达状态,建立 TCGA 队列作为训练集和 ICGC 队列作为验证集。在 TCGA 队列中,按单因素 COX 回归、LASSO 回归和多因素 COX 回归的顺序分析 HCC 组织与肝组织之间的 EMTRGs,并构建 EMTRGs 风险模型。此外,还分析了 TCGA 队列中高低风险组的富集途径、基因突变状态、免疫浸润和药物反应,并验证了 EMTRGs 的蛋白表达状态。结果显示,TCGA 队列中有 286 个差异表达的 EMTRGs,其中 EZH2、S100A9、TNFRSF11B、SPINK5 和 CCL21 用于建模。TCGA 队列中 HCC 患者的高风险组预后较差,ICGC 队列也证实了这一发现。此外,单因素和多因素 COX 回归分析显示,EMTRGs 风险评分是两个队列中独立的预后因素。GSEA 分析结果表明,高风险组中大多数富集途径与肿瘤有关,低风险组中富集的途径主要与代谢有关。不同风险组的患者免疫状况不同,高风险组可能从靶向治疗中获益更多。总之,该研究构建了一个预测 HCC 患者预后的 EMTRGs 风险模型,该模型可能有助于辅助 HCC 患者治疗药物的选择。