Multi-omics analysis reveals a pericyte-associated gene expression signature for predicting prognosis and therapeutic responses in solid cancers

IF 3.4 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics Pub Date : 2024-09-01 DOI:10.1016/j.ygeno.2024.110942

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Abstract

The influence of the stroma on cancer progression has been underestimated, particularly the role of vascular pericytes in the tumor microenvironment. Herein, we identified 51 differentially expressed genes in tumor-derived pericytes (TPCs) by analyzing transcriptomic data from TCGA alongside our proteomic data. Using five key TPC-related genes, we constructed a prognostic risk model that accurately predicts prognosis and treatment responses in liver and lung cancers. Enrichment analyses linked these genes to blood vessel remodeling, function, and immune-related pathways. Single-cell RNA sequencing data from the GEO database validated these findings, showing significant upregulation of AKAP12 and RRAS in TPCs. Immunostaining confirmed increased expression of these genes in liver and lung tumors. Depletion of RRAS or AKAP12 in TPCs restored their blood vessel-supporting role. Overall, our findings suggest that TPC-related gene profiles can predict patient outcomes and therapeutic responses in solid cancers, and targeting these profiles could be an improved treatment strategy.

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多组学分析揭示了用于预测实体瘤预后和治疗反应的包膜相关基因表达特征

基质对癌症进展的影响一直被低估，尤其是血管周细胞在肿瘤微环境中的作用。在本文中，我们通过分析 TCGA 转录组数据和蛋白质组数据，确定了肿瘤源性周细胞（TPC）中 51 个差异表达基因。利用五个关键的TPC相关基因，我们构建了一个预后风险模型，该模型能准确预测肝癌和肺癌的预后和治疗反应。富集分析将这些基因与血管重塑、功能和免疫相关通路联系起来。来自 GEO 数据库的单细胞 RNA 测序数据验证了这些发现，显示 AKAP12 和 RRAS 在 TPCs 中显著上调。免疫染色证实了这些基因在肝脏和肺部肿瘤中的表达增加。TPCs中RRAS或AKAP12的缺失恢复了它们的血管支持作用。总之，我们的研究结果表明，TPC相关基因图谱可以预测实体瘤患者的预后和治疗反应，针对这些图谱可以改进治疗策略。

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

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.