Xia Shenglong, Xu Zhengyang, Cheng Cheng, An Rui, Chen Wenci, Lin Daopo, Gao Yuzhen, Wang Liangjing, Xie Xinyou, Zhang Jun
Department of Clinical Laboratory, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China.
Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, China.
Discov Oncol. 2025 May 10;16(1):721. doi: 10.1007/s12672-025-02522-2.
Metabolic dysregulation was closely associated with cancers. However, there is a lack of studies to explore the relationship between blood metabolites, related proteins, and different types of cancer.
Two-sample Mendelian randomization (MR) analysis was used to assess the causal effects of genetically determined metabolites and metabolite ratios on solid cancers. we analyzed 1400 metabolites/metabolite ratios as exposures and 16 cancers from UK Biobank/FinnGen as outcomes. Protein-metabolite interactions were mapped via MR and visualized with Cytoscape, followed by Gene Ontology enrichment. Clinical validation included metabolomic profiling of 75 breast cancer patients and 20 controls.
MR analysis identified 11 metabolites or metabolite ratios causally associated with cancer risk. Moreover, 48 proteins were demonstrated to be involved in the regulation of these metabolites, which are predominantly enriched in 5 significant metabolic pathways in cancers. Clinically, elevated lignoceroylcarnitine (C24) reduced breast cancer risk, while high glucose-to-mannose and alanine-to-asparagine ratios increased risk.
Our study revealed a causal effects of metabolites and its related proteins/pathways on various types of cancers.
代谢失调与癌症密切相关。然而，缺乏研究来探索血液代谢物、相关蛋白质与不同类型癌症之间的关系。
采用两样本孟德尔随机化（MR）分析来评估基因决定的代谢物和代谢物比率对实体癌的因果效应。我们将1400种代谢物/代谢物比率作为暴露因素，将来自英国生物银行/芬兰基因库的16种癌症作为结局进行分析。通过MR绘制蛋白质-代谢物相互作用图谱，并用Cytoscape进行可视化，随后进行基因本体富集分析。临床验证包括对75例乳腺癌患者和20例对照进行代谢组学分析。
MR分析确定了11种与癌症风险有因果关系的代谢物或代谢物比率。此外，有48种蛋白质被证明参与这些代谢物的调节，它们主要富集于癌症的5条重要代谢途径中。在临床上，木蜡酰肉碱（C24）水平升高可降低乳腺癌风险，而高葡萄糖与甘露糖比率以及高丙氨酸与天冬酰胺比率则会增加风险。
我们的研究揭示了代谢物及其相关蛋白质/途径对各种类型癌症的因果效应。
