A Novel 5-Methylcytosine- and Immune-Related Prognostic Signature Is a Potential Marker of Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common and highly lethal pulmonary interstitial lung disease. The current study is aimed at investigating reliable markers suitable for the treatment and identification of IPF. This study constructed the first 5-methylcytosine- (m5C-) and immune-related prognostic signature (m5CPS) based on coexpressed genes of m5C regulatory genes and immune-related genes. The m5CPS was established using the training cohort ( $n=68$ ) and verified using the test ( $n=44$ ) and validation ( $n=64$ ) cohorts. The area under the curve (AUC) values were utilized to evaluate the accuracy of m5CPS in predicting the survival of IPF patients. The Kaplan-Meier curves and Cox regression analyses were used to assess the prognostic effect of m5CPS. The AUC was utilized to evaluate the reliability of m5CPS in distinguishing IPF patients from healthy individuals. In terms of the results, m5CPS could predict the one-, three-, and five-year survival rates of IPF patients with high accuracy ( $\text{AUC}=.803–.973$ ). In fact, m5CPS is not only an independent indicator of the poor prognosis of IPF patients ( $\text{hazard}\text{ratio}>1$ ; $p<.05$ ) but can also distinguish IPF patients from healthy individuals ( $\text{AUC}=.862$ ). Also, m5CPS may affect the immune response and inflammatory response, and it was positively associated with the infiltration levels of active mast cells ( $p<.05$ ). In sum, the current study establishes a novel m5CPS for IPF and reveals the role of m5CPS as a reliable marker for predicting the prognosis and disease status of IPF patients.