1. Department of Clinical Laboratory, Zhuhai People's Hospital (Zhuhai Hospital affiliated with Jinan University), Zhuhai, Guangdong, China.
2. Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
3. Department of Medical Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
4. Department of Clinical Medical Laboratory, Guangzhou First' People Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
5. Department of Clinical Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
# These authors contributed equally to this work.
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 (m5C) 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 m5C RNA modification.
Results: We found that the m5C modification levels in leukocytes of NSCLC patients were decreased dramatically, which were compared to the normal controls, and levels of m5C modification decreased progressively with tumor stage. Importantly, m5C 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 m5C modification with these serum tumor biomarkers further improved the AUC to 0.960. A nomogram model incorporating m5C modification also provided an effectively diagnostic tool for NSCLC.
Conclusion: Collectively, our findings suggested that m5C modification in leukocytes held promise as a prospective biomarker for NSCLC diagnosis.
Keywords: 5-Methylcytosine, non-small cell lung cancer, leukocytes, diagnosis, biomarker