Molecular Signatures Bidirectionally Link Myocardial Infarction and Lung Cancer

Dr. Dhruva Nandi ¹ Rajiv Janardhanan ¹ Sridhar Hannenhalli ^2* Piyush Agrawal ^1*

• ¹ SRM Institutes for Medical Science, SRM University, Chennai, India
• ² National Cancer Institute Bethesda, Bethesda, Illinois, United States

Myocardial Infarction (MI) and lung cancers substantially contribute 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 linking MI and lung cancer relationship to improve the patient clinical outcomes. Here, we identified common differentially expressed genes between MI and lung cancer. We identified 1496 upregulated and 1482 downregulated genes in MI datasets and based on the 1000 most upregulated and downregulated genes in LUAD and LUSC, we identified 35 genes common across MI, LUAD, and LUSC. Functional enrichment revealed shared biological processes like "inflammatory response", and "cell differentiation". Cox hazard proportional model shows significant association of the shared genes with overall survival of lung cancer patients, as well as with smoking history in lung cancer patients. In addition, machine learning model based on shared genes' expression distinguished MI patients from controls with an AUROC of 0.72 and AUPRC of 0.86. Lastly, 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.