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胃腺癌中乳酰化相关基因集与线粒体功能的综合分析：对预后和治疗策略的影响。

Comprehensive analysis of lactylation-related gene sets and mitochondrial functions in gastric adenocarcinoma: implications for prognosis and therapeutic strategies.

机构信息

Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.

出版信息

Front Immunol. 2024 Oct 16;15:1451725. doi: 10.3389/fimmu.2024.1451725. eCollection 2024.

DOI:10.3389/fimmu.2024.1451725
PMID:39478860
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11521809/
Abstract

Gastric adenocarcinoma (STAD) is characterized by high heterogeneity and aggressiveness, leading to poor prognostic outcomes worldwide. This study explored the prognostic significance of lactylation-related gene sets and mitochondrial functions in STAD by integrating large-scale genomic datasets, including TCGA and several GEO datasets. We utilized Spatial transcriptomics and single-cell RNA sequencing to delineate the tumor microenvironment and assess the heterogeneity of cellular responses within the tumor. Additionally, the study identified distinct molecular subtypes within STAD that correspond with unique survival outcomes and immune profiles, enhancing the molecular classification beyond current paradigms. Prognostic models incorporating these molecular markers demonstrated superior predictive capabilities over existing models across multiple validation datasets. Furthermore, our analysis of immune landscapes revealed that variations in lactylation could influence immune cell infiltration and responsiveness, pointing towards novel avenues for tailored immunotherapy approaches. These comprehensive insights provide a foundation for targeted therapeutic strategies and underscore the potential of metabolic and immune modulation in improving STAD treatment outcomes.

摘要

胃腺癌（STAD）的特点是高度异质性和侵袭性，导致全球预后不良。本研究通过整合大规模基因组数据集，包括 TCGA 和几个 GEO 数据集，探讨了乳酰化相关基因集和线粒体功能在 STAD 中的预后意义。我们利用空间转录组学和单细胞 RNA 测序来描绘肿瘤微环境，并评估肿瘤内细胞反应的异质性。此外，该研究还在 STAD 中确定了不同的分子亚型，这些亚型与独特的生存结果和免疫特征相对应，超越了当前范式的分子分类。纳入这些分子标志物的预后模型在多个验证数据集中表现出优于现有模型的预测能力。此外，我们对免疫景观的分析表明，乳酰化的变化可能影响免疫细胞浸润和反应性，为量身定制的免疫治疗方法开辟了新途径。这些全面的见解为靶向治疗策略提供了基础，并强调了代谢和免疫调节在改善 STAD 治疗结果方面的潜力。

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