BACKGROUND: Immune checkpoint inhibitors (ICIs) have advanced cancer treatment but are associated with serious cardiovascular side effects, including myocarditis, which is challenging to diagnose due to limited specificity of current biomarkers. Rho-associated kinase 2 (ROCK2) may play a role in myocarditis pathogenesis by mediating inflammation and myocardial remodeling. This study investigates the potential of ROCK2 protein detection as a diagnostic marker for ICIs-associated myocarditis. OBJECTIVES: To evaluate ROCK2 protein levels in patients with ICIs-associated myocarditis and assess its diagnostic value, providing insights for improved identification and management of this condition. METHODS: We conducted a study with 10 ICIs-treated gastric cancer patients diagnosed with myocarditis and a control group of 10 similar ICIs-treated patients without myocarditis. ROCK2 levels and inflammatory markers were measured via ELISA, and clinical assessments included cardiac imaging, electrocardiography, and echocardiography. Statistical analysis of group differences used independent t-tests and chi-square tests. RESULTS: ROCK2 expression was significantly higher in myocarditis patients compared to controls (p <
0.001), alongside elevated inflammatory markers, specifically hypersensitive C-reactive protein (hs-CRP), interleukins1β (IL-1β) and IL-17. Diagnostic myocardial markers such as N-terminal pro B-type natriuretic peptide (NT-proBNP), and soluble suppression of tumorigenicity 2 (sST2) also showed substantial elevation. Following treatment discontinuation and glucocorticoid administration, both ROCK2 levels and inflammatory indicators declined. CONCLUSIONS: Elevated ROCK2 protein levels could serve as a promising biomarker for ICIs-associated myocarditis. ROCK2 detection, combined with traditional markers, may enhance diagnostic accuracy. Further studies are warranted to explore ROCK2 inhibition as a potential therapeutic strategy for managing ICIs-associated myocarditis.