Identification of Proteome-Based Immune Subtypes of Early Hepatocellular Carcinoma and Analysis of Potential Metabolic Drivers.

IF 6.1 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Molecular & Cellular Proteomics Pub Date : 2024-01-01 Epub Date: 2023-11-25 DOI:10.1016/j.mcpro.2023.100686

Lihong Diao, Mengqi He, Binsheng Xu, Lanhui Chen, Ze Wang, Yuting Yang, Simin Xia, Shengwei Hu, Shuzhen Guo, Dong Li

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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, ranking fourth in frequency. The relationship between metabolic reprogramming and immune infiltration has been identified as having a crucial impact on HCC progression. However, a deeper understanding of the interplay between the immune system and metabolism in the HCC microenvironment is required. In this study, we used a proteomic dataset to identify three immune subtypes (IM1-IM3) in HCC, each of which has distinctive clinical, immune, and metabolic characteristics. Among these subtypes, IM3 was found to have the poorest prognosis, with the highest levels of immune infiltration and T-cell exhaustion. Furthermore, IM3 showed elevated glycolysis and reduced bile acid metabolism, which was strongly correlated with CD8 T cell exhaustion and regulatory T cell accumulation. Our study presents the proteomic immune stratification of HCC, revealing the possible link between immune cells and reprogramming of HCC glycolysis and bile acid metabolism, which may be a viable therapeutic strategy to improve HCC immunotherapy.

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早期肝细胞癌蛋白质组免疫亚型鉴定及潜在代谢驱动因素分析

肝细胞癌(HCC)是全球癌症相关死亡的主要原因，发病率排名第四。代谢重编程和免疫浸润之间的关系已被确定为对HCC进展具有重要影响。然而，需要对肝细胞癌微环境中免疫系统和代谢之间的相互作用有更深入的了解。在这项研究中，我们使用蛋白质组学数据集来鉴定HCC中的三种免疫亚型(IM1-IM3)，每种亚型都具有独特的临床、免疫和代谢特征。在这些亚型中，IM3预后最差，免疫浸润和t细胞衰竭水平最高。此外，IM3表现出糖酵解升高和胆汁酸代谢降低，这与CD8 T细胞耗竭和调节性T细胞积累密切相关。我们的研究提出了HCC的蛋白质组免疫分层，揭示了免疫细胞与HCC糖酵解和胆汁酸代谢重编程之间的可能联系，这可能是改善HCC免疫治疗的可行治疗策略。

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

Molecular & Cellular Proteomics 生物-生化研究方法

CiteScore

11.50

自引率

4.30%

发文量

131

审稿时长

84 days

期刊介绍： The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action. The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data. Scope: -Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights -Novel experimental and computational technologies -Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes -Pathway and network analyses of signaling that focus on the roles of post-translational modifications -Studies of proteome dynamics and quality controls, and their roles in disease -Studies of evolutionary processes effecting proteome dynamics, quality and regulation -Chemical proteomics, including mechanisms of drug action -Proteomics of the immune system and antigen presentation/recognition -Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease -Clinical and translational studies of human diseases -Metabolomics to understand functional connections between genes, proteins and phenotypes