Department of Emergency, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Medicine (Baltimore). 2024 Mar 8;103(10):e37314. doi: 10.1097/MD.0000000000037314.
Stomach adenocarcinoma (STAD) is a one of most common malignancies with high mortality-to-incidence ratio. Programmed cell death (PCD) exerts vital functions in the progression of cancer. The role of PCD-related genes (PRGs) in STAD are not fully clarified. Using TCGA, GSE15459, GSE26253, GSE62254 and GSE84437 datasets, PCD-related signature (PRS) was constructed with an integrative procedure including 10 machine learning methods. The role of PRS in predicting the immunotherapy benefits was evaluated by several predicting score and 3 immunotherapy datasets (GSE91061, GSE78220, and IMvigor210). The model developed by Lasso + CoxBoost algorithm having a highest average C-index of 0.66 was considered as the optimal PRS. As an independent risk factor for STAD patients, PRS had a good performance in predicting the overall survival rate of patients, with an AUC of 1-, 3-, and 5-year ROC curve being 0.771, 0.751 and 0.827 in TCGA cohort. High PRS score demonstrated a lower gene set score of some immune-activated cells and immune-activated activities. Patient with high PRS score had a higher TIDE score, higher immune escape score, lower PD1&CTLA4 immunophenoscore, lower TMB score, lower response rate and poor prognosis, indicating a less immunotherapy response. The IC50 value of some drugs correlated with chemotherapy and targeted therapy was higher in high PRS score group. Our investigation developed an optimal PRS in STAD and it acted as an indicator for predicting the prognosis, stratifying risk and guiding treatment for STAD patients.
胃腺癌 (STAD) 是一种最常见的恶性肿瘤之一，其死亡率与发病率之比很高。程序性细胞死亡 (PCD) 在癌症的发展中发挥着重要作用。PCD 相关基因 (PRGs) 在 STAD 中的作用尚未完全阐明。本研究使用 TCGA、GSE15459、GSE26253、GSE62254 和 GSE84437 数据集，通过包括 10 种机器学习方法的综合程序构建了 PCD 相关特征 (PRS)。通过几种预测评分和 3 个免疫治疗数据集 (GSE91061、GSE78220 和 IMvigor210) 评估了 PRS 预测免疫治疗获益的作用。Lasso+CoxBoost 算法构建的模型具有最高的平均 C 指数 0.66，被认为是最佳 PRS。作为 STAD 患者的独立危险因素，PRS 在预测患者总生存率方面表现良好，TCGA 队列中 1 年、3 年和 5 年 ROC 曲线的 AUC 分别为 0.771、0.751 和 0.827。高 PRS 评分表明一些免疫激活细胞和免疫激活活性的基因集评分较低。高 PRS 评分的患者 TIDE 评分较高、免疫逃逸评分较高、PD1&CTLA4 免疫表型评分较低、TMB 评分较低、应答率较低、预后较差，表明免疫治疗反应较差。高 PRS 评分组中一些与化疗和靶向治疗相关的药物的 IC50 值较高。本研究开发了 STAD 的最佳 PRS，可作为预测预后、分层风险和指导 STAD 患者治疗的指标。
