Prognostic value of tripartite motif (TRIM) family gene signature from bronchoalveolar lavage cells in idiopathic pulmonary fibrosis

Abstract

Background: Tripartite motif (TRIM) family genes get involved in the pathogenesis and development of various biological processes; however, the prognostic value of TRIM genes for idiopathic pulmonary fibrosis (IPF) needs to be explored. Methods: We acquired gene expression based on bronchoalveolar lavage (BAL) cells and clinical data of three independent IPF cohorts in the GSE70866 dataset from the Gene expression omnibus (GEO) database. Differentially expressed TRIM genes (DETGs) between IPF patients and healthy donors were identified and used to establish a risk signature by univariate and multivariate Cox regression analysis in the training cohort. The risk signature was further validated in other IPF cohorts, and compared with previously published signatures. Moreover, we performed functional enrichment analysis to explore the potential mechanisms. Eventually, the quantitative real time PCR was conducted to validate the expressions of the key genes in BAL from 12 IPF patients and 12 non-IPF controls from our institution. Results: We identified 4 DETGs including TRIM7, MEFV, TRIM45 and TRIM47 significantly associated with overall survival (OS) of IPF patients (P < 0.05). A multiple stepwise Cox regression analysis was performed to construct a 4-TRIM-gene prognostic signature. We categorized IPF patients into one low-risk group and the other high-risk group as per the average risk value of the TRIM prognostic signature in the training and validation cohorts. The IPF individuals in the low-risk group demonstrated an obvious OS advantage compared with the high-risk one (P < 0.01). The time-dependent receiver operating characteristic approach facilitated the verification of the predictive value of the TRIM prognostic signature in the training and validation cohorts, compared with other published signatures. A further investigation of immune cells and IPF survival displayed that higher proportion of resting memory CD4+ T cells and resting mast cells harbored OS advantage over lower proportion, however lower proportion of neutrophils, activated dendritic cells and activated NK cells indicated worse prognosis. Conclusion: The TRIM family genes are significant for the prognosis of IPF and our signature could serve as a robust model to predict OS.