Metabolic and immune-related gene signatures: Predictive stratification and prognostic implications in gastric cancer

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Gene Medicine Pub Date : 2023-11-20 DOI:10.1002/jgm.3635

Jian Shao, Wenjia Zhang, Yiguang Li, Yi Tang, Lihong Fan

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Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.

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代谢和免疫相关基因特征:胃癌的预测分层和预后意义。

背景:胃癌以其异质性为特征，表现出不同的分子亚型和临床轨迹。本研究探讨了代谢和免疫驱动通路在胃癌中的意义，构建了基于差异表达的代谢和免疫相关基因(DE-MIGs)的预后特征。方法:代谢和免疫相关基因来源于GeneCards数据库。使用limma软件包对TCGA-STAD数据集进行差异表达分析，揭示了51个进行功能富集审查的de - migg。LASSO Cox回归方法指导预后特征的创建，并确定个体患者风险评分。使用CIBERSORT、ESTIMATE和ssGSEA等评估工具来研究免疫微环境，同时在不同的特征分类中仔细检查突变谱、基因组稳定性、化疗耐药性和免疫治疗反应性。结果:在鉴定的DE-MIGs中，26个与胃癌患者的总生存期显著相关。发达的预后特征熟练地将患者分为高风险和低风险队列，后者表现出明显更好的结果。该研究强调了免疫微环境在影响胃癌预后中的中心地位。高危组以tgf - β、TP53和NRF2等关键通路为主，低危组以LRTK-RAS和WNT通路为主。有趣的是，低风险部分也表现出更高的肿瘤突变负担和对免疫治疗的易感性。结论:我们的研究结果引入了一个关键的预后特征，植根于DE-MIGs，有效地将胃癌患者划分为不同的基于风险的部分。了解免疫微环境在胃癌进展中的影响作用为更精细的治疗干预铺平了道路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.