Diagnostic value of aberrant decreased 5-Methylcytosine RNA modification in leukocytes for non-small cell lung cancer

Background: Non-small cell lung cancer (NSCLC) was a disease with poor outcomes, partly because there were no high-efficiency non-invasive diagnostic biomarkers. The RNA modification status of 5-Methylcytosine (m(5)C) has been shown to be a biomarker for various diseases, but its potentiality to be a diagnostic biomarker for NSCLC remained inconclusive. Methods: In this research, we collected peripheral leukocyte samples from 141 patients with NSCLC and 90 normal people as controls to evaluate the extent of m(5)C RNA modification. Results: We found that the m(5)C modification levels in leukocytes of NSCLC patients were decreased dramatically, which were compared to the normal controls, and levels of m(5)C modification decreased progressively with tumor stage. Importantly, m(5)C modification exhibited superior diagnostic value compared to carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), and carbohydrate antigen 125 (CA125), which demonstrated area under the curves (AUCs) of 0.912, 0.773, 0.669, 0.754, and 0.732, respectively. The combination of m(5)C modification with these serum tumor biomarkers further improved the AUC to 0.960. A nomogram model incorporating m(5)C modification also provided an effectively diagnostic tool for NSCLC. Conclusion: Collectively, our findings suggested that m(5)C modification in leukocytes held promise as a prospective biomarker for NSCLC diagnosis.