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结合空间代谢组学和4D-DIA定量蛋白质组学方法探索肺癌与心脏之间的关系。

Combined spatial metabolomics and 4D-DIA quantitative proteomics approaches to explore the relationship between lung cancer and the heart.

作者信息

Bai Tingting, Wan Quan, Yue Changcheng, Wang Jingjing, Deng Shichao, Shen Xueying, Wang Hongqing, Huang Liyan, Wang Dong

机构信息

Inner Mongolia Medical University, Hohhot, Inner Mongolia, People's Republic of China.

Affiliated Hospital of Inner Mongolia Minzu University, No.1742 East Hollinghe Street, Tongliao, 028000, Inner Mongolia, People's Republic of China.

出版信息

Sci Rep. 2025 Apr 28;15(1):14878. doi: 10.1038/s41598-025-97821-7.

DOI:10.1038/s41598-025-97821-7
PMID:40295682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12037715/
Abstract

Lung cancer and cardiovascular disease pose persistent threats to human health, despite advancements in targeted therapy, percutaneous coronary intervention, and drug treatments. Challenges such as side effects, drug resistance, hospitalization rates, and mortality remain high. These diseases are closely linked, sharing common risk factors and intricately influencing each other. This study aims to investigate the interplay between lung disease and cardiovascular disease by examining changes in cardiac metabolites and protein expression using spatial metabolomics and 4D-DIA quantitative proteomics approaches in the setting of lung cancer. Nude mice were selected and A549 cells were injected axillary and metabolomics was used to observe the alterations in cardiac metabolism in the setting of lung cancer in nude mice.The findings reveal well-defined tumor structures. Further, spatial mass spectrometry imaging analysis demonstrates distinct metabolite distributions across cardiac regions, indicating significant differences between control and model groups. Through spatial metabolomics and proteomics analyses, key differential metabolites such as Gln-His-Val-Glu, LysoPC 22:6, and LPC (20:2/0:0), primarily amino acids, and glycerophospholipids, as well as differential proteins including Mknk1, Trafd1, Dab2ip, Tab1, Ripk3, G3PDH, and Mapk15, are identified. These results underscore the crucial role of these factors in cardiovascular injury. This study elucidates the intricate link between lung cancer and cardiovascular disease and identifies altered metabolites and proteins in the heart within a lung cancer environment. These insights are pivotal for informing future treatments and interventions for both diseases.

摘要

尽管在靶向治疗、经皮冠状动脉介入治疗和药物治疗方面取得了进展,但肺癌和心血管疾病仍然对人类健康构成持续威胁。副作用、耐药性、住院率和死亡率等挑战仍然很高。这些疾病紧密相连,具有共同的风险因素,并相互产生复杂的影响。本研究旨在通过在肺癌背景下使用空间代谢组学和4D-DIA定量蛋白质组学方法检测心脏代谢物和蛋白质表达的变化,来研究肺部疾病和心血管疾病之间的相互作用。选择裸鼠,将A549细胞注射到腋窝,利用代谢组学观察裸鼠肺癌背景下心脏代谢的变化。研究结果显示出明确的肿瘤结构。此外,空间质谱成像分析表明心脏各区域的代谢物分布不同,表明对照组和模型组之间存在显著差异。通过空间代谢组学和蛋白质组学分析,确定了关键的差异代谢物,如Gln-His-Val-Glu、溶血磷脂酰胆碱22:6和LPC(20:2/0:0),主要是氨基酸和甘油磷脂,以及差异蛋白质,包括Mknk1、Trafd1、Dab2ip、Tab1、Ripk3、G3PDH和Mapk15。这些结果强调了这些因素在心血管损伤中的关键作用。本研究阐明了肺癌和心血管疾病之间的复杂联系,并确定了肺癌环境中心脏内代谢物和蛋白质的变化。这些见解对于为这两种疾病的未来治疗和干预提供信息至关重要。

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