DataSheet_1_A pyroptosis-related gene signature for prognosis prediction in hepatocellular carcinoma.pdf

IntroductionHepatocellular carcinoma (HCC) is one of the most invasive cancers with a low 5-year survival rate. Pyroptosis, a specialized form of cell death, has shown its association with cancer progression. However, its role in the prognosis of HCC has not been fully understood.MethodsIn our study, clinical information and mRNA expression for 1076 patients with HCC were obtained from the five public cohorts. Pyroptotic clusters were generated by unsupervised clustering based on 40 pyroptosis-related genes (PRGs) in the TCGA and ICGC cohort. A pyroptosis-related signature was constructed using least absolute shrinkage and selection operator (LASSO) regression according to differentially expressed genes (DEGs) of pyroptotic clusters. The signature was then tested in the validation cohorts (GES10142 and GSE14520) and subsequently validated in the CPTAC cohort (n=159) at both mRNA and protein levels. Response to sorafenib was explored in GSE109211.ResultsThree clusters were identified based on the 40 PRGs in the TCGA cohort. A total of 24 genes were selected based on DEGs of the above three pyroptotic clusters to construct the pyroptotic risk score. Patients with the high-risk score showed shorter overall survival (OS) compared to those with the low-risk score in the training set (P

肝细胞癌（HCC）为侵袭性极强的癌症之一，其五年生存率较低。细胞焦亡，一种特殊的细胞死亡形式，已被证实与癌症进展密切相关。然而，其在肝细胞癌预后中的作用尚未得到充分理解。研究方法：本研究中，我们收集了来自五个公开队列的1076例肝细胞癌患者的临床信息和mRNA表达数据。通过基于TCGA和ICGC队列中40个细胞焦亡相关基因（PRGs）的无监督聚类，生成了细胞焦亡簇。根据细胞焦亡簇的差异表达基因（DEGs），利用最小绝对收缩和选择算子（LASSO）回归构建了细胞焦亡相关特征。该特征随后在验证队列（GES10142和GSE14520）中进行测试，并在CPTAC队列（n=159）中进行了mRNA和蛋白质水平的验证。在GSE109211队列中探讨了索拉非尼的响应。研究结果：基于TCGA队列中的40个PRGs，确定了三个簇。根据上述三个细胞焦亡簇的DEGs，选择了24个基因构建细胞焦亡风险评分。与低风险评分患者相比，高风险评分患者在训练集中显示出更短的总体生存期（OS）（P