Jiangzhong Pharmaceutical Co., Ltd., Nanchang, China.
National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Nanchang, China.
J Gene Med. 2024 Jan;26(1):e3635. doi: 10.1002/jgm.3635. Epub 2023 Nov 20.
Gastric cancer, marked by its heterogeneous nature, showcases various molecular subtypes and clinical trajectories. This research delves into the significance of metabolic and immune-driven pathways in gastric cancer, constructing a prognostic signature derived from differentially expressed metabolic and immune-correlated genes (DE-MIGs).
Metabolic and immune-associated gene were sourced from the GeneCards database. Differential expression analysis on the TCGA-STAD dataset was executed using the limma package, unveiling 51 DE-MIGs that underwent functional enrichment scrutiny. The LASSO Cox regression methodology guided the creation of the prognostic signature, and individual patient risk scores were determined. Assessment tools like CIBERSORT, ESTIMATE and ssGSEA were deployed to study the immune microenvironment, while mutation profiles, genomic stability, resistance to chemotherapy and immunotherapy responsiveness were scrutinized across distinct signature categorizations.
Among the identified DE-MIGs, 26 were significantly tied to the overall survival of gastric cancer patients. The developed prognostic signature proficiently differentiated patients into high-risk and low-risk cohorts, with the latter showing markedly better outcomes. The study underscored the centrality of the immune microenvironment in influencing gastric cancer outcomes. Key pathways such as TGF-Beta, TP53 and NRF2 dominated the high-risk group, whereas the LRTK-RAS and WNT pathways characterized the low-risk group. Interestingly, the low-risk segment also manifested a heightened tumor mutation burden and enhanced susceptibility to immunotherapy.
Our findings introduce a pivotal prognostic signature, rooted in DE-MIGs, that effectively segregates gastric cancer patients into distinct risk-based segments. Insights into the influential role of the immune microenvironment in gastric cancer progression pave the way for more refined therapeutic interventions.
胃癌具有异质性，表现出多种分子亚型和临床轨迹。本研究探讨了代谢和免疫驱动途径在胃癌中的意义，构建了一个源自差异表达代谢和免疫相关基因（DE-MIGs）的预后特征。
代谢和免疫相关基因源自 GeneCards 数据库。使用 limma 包对 TCGA-STAD 数据集进行差异表达分析，揭示了 51 个经历功能富集分析的 DE-MIGs。LASSO Cox 回归方法指导了预后特征的创建，并确定了个体患者的风险评分。使用 CIBERSORT、ESTIMATE 和 ssGSEA 等评估工具研究免疫微环境，同时在不同特征分类中研究突变谱、基因组稳定性、对化疗和免疫治疗的耐药性。
在鉴定的 DE-MIGs 中，有 26 个与胃癌患者的总体生存率显著相关。所开发的预后特征能够将患者准确地分为高风险和低风险组，后者的预后明显更好。该研究强调了免疫微环境在影响胃癌结果中的核心作用。关键途径如 TGF-Beta、TP53 和 NRF2 主导高风险组，而 LRTK-RAS 和 WNT 途径则代表低风险组。有趣的是，低风险组还表现出更高的肿瘤突变负担和对免疫治疗的更高敏感性。
我们的发现引入了一个重要的预后特征，其基于 DE-MIGs，能够有效地将胃癌患者分为不同的风险组。对免疫微环境在胃癌进展中的影响作用的深入了解为更精细的治疗干预铺平了道路。
