Wang Ruiyu, Huang Shu, Wang Ping, Luo Rui, Wang Yizhou, Shi Xiaomin, Zhang Wei, Shi Lei, Zhou Xian, Tang Xiaowei
Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, China.
Department of Gastroenterology, Lianshui County People's Hospital, Huai'an, China.
Transl Cancer Res. 2025 Jul 30;14(7):4080-4099. doi: 10.21037/tcr-2024-2660. Epub 2025 Jul 25.
Gastric cancer (GC) is a prevalent malignancy with high morbidity and mortality. Pyroptosis, a form of programmed cell death, plays a significant role in cancer progression and immune regulation. This study aimed to construct a pyroptosis-related prognostic signature (PRPS) and analyze its association with the tumor microenvironment in GC by integrating single-cell and bulk RNA sequencing data.
Pyroptosis-related differentially expressed genes in GC were identified by integrating single-cell and bulk RNA sequencing data. The PRPS was constructed using univariate and multivariate Cox regression analyses, and evaluated by Kaplan-Meier curves, receiver operating characteristic curves, and nomogram analysis. Subsequently, genomic variations, immune landscapes, immune checkpoint inhibitors (ICIs) responses, and drug sensitivity were evaluated in different risk subgroups.
We constructed a PRPS in GC by integrating single-cell and bulk RNA sequencing data. The PRPS exhibited strong predictive efficiency, with the high-risk group showing significantly lower overall survival, progression-free survival, and disease-specific survival. Multivariate Cox regression validated the PRPS as an independent prognostic factor, while the PRPS-based nomogram showed high predictive accuracy. Functional enrichment and immune landscape analysis revealed the differences between the risk subgroups in immune pathways, gene mutations, immune cell infiltration, and tumor mutational burden. Analysis of ICIs responses and drug sensitivity showed the differences in treatment among different risk subgroups, providing a basis for personalized treatment.
The PRPS provides a promising tool for the prognostic prediction, targeted prevention, and personalized treatment for GC, and may promote the precision medicine for GC patients.
胃癌（GC）是一种发病率和死亡率都很高的常见恶性肿瘤。细胞焦亡作为一种程序性细胞死亡形式，在癌症进展和免疫调节中发挥着重要作用。本研究旨在通过整合单细胞和批量RNA测序数据，构建一种与细胞焦亡相关的预后特征（PRPS），并分析其与胃癌肿瘤微环境的关联。
通过整合单细胞和批量RNA测序数据，鉴定胃癌中与细胞焦亡相关的差异表达基因。使用单变量和多变量Cox回归分析构建PRPS，并通过Kaplan-Meier曲线、受试者工作特征曲线和列线图分析进行评估。随后，在不同风险亚组中评估基因组变异、免疫图谱、免疫检查点抑制剂（ICI）反应和药物敏感性。
我们通过整合单细胞和批量RNA测序数据构建了胃癌的PRPS。PRPS显示出强大的预测效率，高危组的总生存期、无进展生存期和疾病特异性生存期显著更低。多变量Cox回归验证PRPS为独立的预后因素，而基于PRPS的列线图显示出高预测准确性。功能富集和免疫图谱分析揭示了风险亚组在免疫途径、基因突变、免疫细胞浸润和肿瘤突变负担方面的差异。ICI反应和药物敏感性分析显示不同风险亚组在治疗上存在差异，为个性化治疗提供了依据。
PRPS为胃癌的预后预测、靶向预防和个性化治疗提供了一个有前景的工具，并可能推动胃癌患者的精准医学发展。
