HLA-DQB1 expression on tumor cells is a novel favorable prognostic factor for relapse in early-stage lung adenocarcinoma
Authors Zhang L, Li M, Deng B, Dai N, Feng Y, Shan J, Yang Y, Mao C, Huang P, Xu C, Wang D
Received 11 December 2018
Accepted for publication 19 February 2019
Published 1 April 2019 Volume 2019:11 Pages 2605—2616
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Antonella D'Anneo
Liang Zhang,1 Mengxia Li,1 Bo Deng,2 Nan Dai,1 Yan Feng,1 Jinlu Shan,1 Yuxin Yang,1 Chengyi Mao,3 Ping Huang,1 Chengxiong Xu,1 Dong Wang1
1Cancer Center of Daping Hospital, Third Military Medical University, Chongqing 400042, People’s Republic of China; 2Thoracic Surgery Department of Daping Hospital, Third Military Medical University, Chongqing 400042, People’s Republic of China; 3Pathology Department of Daping Hospital, Third Military Medical University, Chongqing 400042, People’s Republic of China
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) 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 anti-tumor immune activity.
Keywords: HLA-DQB1, lung adenocarcinoma, tumor recurrence, prognostic factor
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