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

BackgroundImmune 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 methodsMitophagy 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.ResultsA total of 4 mitophagy key genes in ICIs-related myocarditis were identified by combining multiple bioinformatics analysis methods: AW112010, Igfbp7, Tmsb4x, Ost4.

The expression levels of mitophagy key genes in the ICIs-related myocarditis group were significantly higher than those in the normal group (P < 0.05 or P < 0.01), and both had high diagnostic value.