HLA-DQB1 expression on tumor cells is a novel favorable prognostic factor for relapse in early-stage lung adenocarcinoma

Abstract

Background: Postoperative recurrence is the main cause of a poor prognosis in early-stage lung adenocarcinoma (LUAD). Factors that can predict recurrence risk are critically needed. Materials and methods: In this study, we designed a screening procedure based on gene profile data and performed validation using TCGA and Daping hospital’s cohorts. Differentially expressed genes (DEGs) between patients with recurrence-free survival (RFS) <1 year and RFS >3 years were identified, overlapping genes among these DEGs were selected as candidate biomarkers. A Cox proportional hazards model, immunohistochemistry and Kaplan-Meier survival analysis were performed to validate these biomarkers in two distinct validation sets. Results: SFTPB, SFTPD, SFTA1P, HLA-DQB1, ITGB8, ANLN, and LRRN1 were overlapped both in TCGA and Daping discovery sets. The Cox proportional hazards model analysis of the TCGA validation set showed that HLA-DQB1 was an independent prognostic factor for RFS (HR=0.686, 95% CI, 0.542-0.868). Immunohistochemistry and Kaplan-Meier analysis in Daping validation sets confirmed HLA-DQB1 expression on tumor cells (not interstitial cells) to be an effective predictor of postoperative recurrence. Further examination revealed that the level of HLA-DQB1 expression on tumor cells was positively correlated with CD4- and CD8-positive lymphocyte infiltration into the tumor. Conclusion: All results indicate that high expression of HLA-DQB1 on tumor cells is a good prognostic marker in early-stage LUAD, and the mechanism may be related to antitumor immune activity.