Molecular signatures bidirectionally link myocardial infarction and lung cancer

TL;DR

This study finds shared genes and biological processes between heart attacks and lung cancer, suggesting potential new treatments for both conditions.

Contribution

The study identifies 35 shared genes and proposes drug repurposing for treating both MI and lung cancer.

Findings

35 genes are commonly dysregulated in MI, LUAD, and LUSC.

Shared genes are linked to survival and smoking history in lung cancer patients.

A machine learning model using shared genes distinguishes MI patients from controls with high accuracy.

Abstract

Myocardial Infarction (MI) and lung cancers are major contributors to mortality worldwide. While seemingly diverse, the two share common risk factors, such as smoking and hypertension. There is a pressing need to identify bidirectional molecular signatures that link MI and lung cancer, in order to improve clinical outcomes for patients. In this study, we identified common differentially expressed genes between MI and lung cancer. Specifically, we identified 1,496 upregulated and 1,482 downregulated genes in the MI datasets. By focusing on the 1,000 most upregulated and downregulated genes in Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LUSC), we identified 35 genes that are common across MI, LUAD, and LUSC. Functional enrichment analysis revealed shared biological processes, such as “inflammatory response” and “cell differentiation.” The Cox proportional hazards model demonstrated a significant association between the shared genes and overall survival in lung cancer patients, as well as with smoking history in these patients. In addition, a machine learning model based on the expression of the shared genes distinguished MI patients from controls, achieving an AUROC of 0.72 and an AUPRC of 0.86. Finally, based on drug repurposing analysis, we proposed FDA-approved drugs potentially targeting the upregulated genes as novel therapeutic options for the co-occurring conditions of MI and lung cancer. Overall, our findings highlight the similarities in molecular makeup between lung cancer and MI.

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