Combining multi-omics analysis methods to identify biomarkers for mitophagy involved in immune checkpoint inhibitors-related myocarditis

Background: Immune checkpoint inhibitors (ICIs) are prone to induce cardiovascular adverse reactions during the immunotherapy of cancer patients, among which ICIs-related myocarditis is the most severe. Mitophagy dysregulation is associated with various heart diseases, but its role in ICIs-related myocarditis remains unclear. Materials and methods: Mitophagy key genes in ICIs-related myocarditis were screened based on the single-cell RNA sequencing and bulk RNA sequencing data, and their expression levels and diagnostic value were verified. Meanwhile, the key genes, trajectory analysis and cell interaction were validated at the single-cell level. Finally, the myocardial injury markers, cardiac function indicators, histopathological analysis and mitophagy key genes were verified by constructing a mouse model of ICIs-related myocarditis. Results: < 0.01). Conclusion: Mitophagy is involved in the pathogenesis of ICIs-related myocarditis, and AW112010, Igfbp7, Tmsb4x and Ost4 may become potential biomarkers for future clinical practice.