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

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.