Construction of a 5-methylcytosine-Related Molecular Signature to Inform the Prognosis and Immunotherapy of Lung Squamous Cell Carcinoma.

Background: Methylation of cytosine residues resulting in 5-methylcytosine (5-mC) is an important epigenetic modification associated with tumorigenesis. The present study explored the relationship between methylation, prognosis, and immunotherapy of patients suffering from lung squamous cell carcinoma (LUSC).
Methods: RNA sequencing data and corresponding clinical information were downloaded, and preprocessed, and unsupervised consistent cluster analysis was used to identify 5-mC-related clusters and gene clusters. 5-mC scores were calculated using principal component analysis, and a Boruta algorithm was used to evaluate the relationship between tumor mutation burden (TMB), immune checkpoint inhibitor response, and prognosis of individual LUSC patients.
Results: : Two 5-mC clusters and three gene clusters with different prognoses were identified. Patients with higher 5-mC scores showed worse prognoses, which was confirmed in multiple cohorts. Some immune-related biological functions and pathways were enriched in the high-5-mC score subtype.
Conclusion: The 5-mC score is a potential biomarker independent of TMB, which can be a decisive factor regarding immune treatment responses. Further, patients with low 5-mC scores may respond better to immunotherapy. The 5-mC score can thus be used as a potential biomarker for the prognosis of LUSC patients and their response to immunotherapy.