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泛癌症转录组分析确定了 6 类免疫衰老基因,揭示了衰老、免疫系统和癌症之间的分子联系。

Pan-cancer transcriptomic analysis identified six classes of immunosenescence genes revealed molecular links between aging, immune system and cancer.

机构信息

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.

出版信息

Genes Immun. 2023 Apr;24(2):81-91. doi: 10.1038/s41435-023-00197-9. Epub 2023 Feb 17.

Abstract

Aging is a complex process that significantly impacts the immune system. The aging-related decline of the immune system, termed immunosenescence, can lead to disease development, including cancer. The perturbation of immunosenescence genes may characterize the associations between cancer and aging. However, the systematical characterization of immunosenescence genes in pan-cancer remains largely unexplored. In this study, we comprehensively investigated the expression of immunosenescence genes and their roles in 26 types of cancer. We developed an integrated computational pipeline to identify and characterize immunosenescence genes in cancer based on the expression profiles of immune genes and clinical information of patients. We identified 2218 immunosenescence genes that were significantly dysregulated in a wide variety of cancers. These immunosenescence genes were divided into six categories based on their relationships with aging. Besides, we assessed the importance of immunosenescence genes in clinical prognosis and identified 1327 genes serving as prognostic markers in cancers. BTN3A1, BTN3A2, CTSD, CYTIP, HIF1AN, and RASGRP1 were associated with ICB immunotherapy response and served as prognostic factors after ICB immunotherapy in melanoma. Collectively, our results furthered the understanding of the relationship between immunosenescence and cancer and provided insights into immunotherapy for patients.

摘要

衰老是一个复杂的过程,会对免疫系统产生重大影响。免疫系统的衰老相关衰退,称为免疫衰老,可能导致疾病的发展,包括癌症。免疫衰老基因的扰动可能可以描述癌症与衰老之间的关联。然而,泛癌中免疫衰老基因的系统特征在很大程度上仍未得到探索。在这项研究中,我们全面研究了免疫衰老基因在 26 种癌症中的表达及其作用。我们开发了一个综合的计算管道,基于免疫基因的表达谱和患者的临床信息,来识别和描述癌症中的免疫衰老基因。我们确定了 2218 个在各种癌症中显著失调的免疫衰老基因。这些免疫衰老基因根据它们与衰老的关系分为六类。此外,我们评估了免疫衰老基因在临床预后中的重要性,并确定了 1327 个在癌症中作为预后标志物的基因。BTN3A1、BTN3A2、CTSD、CYTIP、HIF1AN 和 RASGRP1 与黑色素瘤的 ICB 免疫治疗反应相关,并在 ICB 免疫治疗后成为预后因素。总的来说,我们的结果进一步了解了免疫衰老和癌症之间的关系,并为患者的免疫治疗提供了思路。

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