Purine metabolism: a pan-cancer metabolic dysregulation across circulation and tissues

IF 33.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2025-10-14 DOI:10.1186/s12943-025-02482-9

Mengjie Yu, Cheng Liu, Minmin Cao, Dou Yang, Tongshan Wang, Jing Xu, Danxia Zhu, Guangji Wang, Jiye Aa, Wei Zhu

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Abstract

Tumors function as organ-like entities within complex ecosystems, interacting with diverse components of their microenvironment, including blood and lymphatic vessels, neurons, immune cells, metabolites, and cytokines, to drive tumorigenesis and progression. Our pan-cancer study investigated the universal tumor hallmarks, integrating metabolite characteristics with molecular mechanisms. Metabolomic profiling on plasma from 2,561 patients across 20 cancer types and 604 healthy controls in two clinical centers, identified three biomarkers in pan cancers: elevated levels of hypoxanthine and reduced levels of cysteine and pyruvic acid. Given the profound significance of hypoxanthine, we further discovered 33 core purine metabolism-related genes in The Cancer Genome Atlas (TCGA) pan-cancer tissues, and their influences on immunomodulation and overall survival. Lastly, candidate therapeutic compounds, intervening purine metabolism, were proposed based on pharmaco-transcriptomics and pharmaco-proteomics analysis. Through interdisciplinary multi-omics investigations, such approaches may enhance insight into antitumor immunotherapy by targeting cancer metabolic reprogramming.

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嘌呤代谢：跨循环和组织的泛癌症代谢失调

肿瘤作为复杂生态系统中的器官样实体，与其微环境的不同组成部分相互作用，包括血液和淋巴管、神经元、免疫细胞、代谢物和细胞因子，以驱动肿瘤的发生和发展。我们的泛癌症研究调查了普遍的肿瘤特征，将代谢物特征与分子机制结合起来。对来自两个临床中心的20种癌症类型的2561名患者和604名健康对照者的血浆进行代谢组学分析，确定了所有癌症的三种生物标志物：次黄嘌呤水平升高，半胱氨酸和丙酮酸水平降低。鉴于次黄嘌呤的深远意义，我们进一步在the Cancer Genome Atlas （TCGA）泛癌组织中发现了33个嘌呤代谢相关核心基因，以及它们对免疫调节和总体生存的影响。最后，基于药物转录组学和药物蛋白质组学分析，提出了干预嘌呤代谢的候选治疗化合物。通过跨学科的多组学研究，这些方法可以通过靶向癌症代谢重编程来增强抗肿瘤免疫治疗的洞察力。

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 Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.