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J Cancer. 2018 Sep 8;9(19):3489-3499. doi: 10.7150/jca.26155. eCollection 2018.

Prognostic value of PD-L1 expression in resected lung adenocarcinoma and potential molecular mechanisms.

Author information

1
Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
2
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin150081, China.
3
Department of Medical oncology, Heilongjiang Provincial Hospital, Harbin, 150000, China.

Abstract

Background: The prognostic role of PD-L1 expression in surgically resected lung adenocarcinoma (ADC) remains controversial. The present study was aimed to clarify the role of PD-L1 expression in predicting prognosis and to investigate its biological function in ADC. Materials and Methods: The association between PD-L1 expression and clinical outcomes in patients with resected ADC was analyzed using immunohistochemistry (IHC) in our cohort (n=104), externally validated by a meta-analysis of 13 published studies. The biological role of PD-L1 in ADC was explored using gene set enrichment analysis (GSEA). Results: Positive PD-L1 expression in tumor cells was observed in 38.5% (40/104). High PD-L1 expression levels were significantly correlated with poor overall survival (P=0.008). Furthermore, the meta-analysis also showed that positive PD-L1 expression was associated with shorter OS than negative PD-L1 expression (HR= 1.75, 95% CI: 1.26-2.42; P<0.001). In subgroup analysis stratified according to ethnicity, the pooled results demonstrated that increased PD-L1 expression was an unfavorable prognostic factor for Asian populations (HR= 2.11, 95% CI: 1.48-3.02; P<0.001), but not for non-Asian populations (HR=1.16, 95% CI: 0.63-2.11, P=0.64). The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with positive lymph node metastasis (OR=1.74, 95% CI: 1.23-2.46; P=0.002) and male (OR=1.56, 95% CI: 1.02-2.37; P=0.04). GSEA revealed PD-L1 expression levels positively correlated with immune process or immune-related pathways. Conclusion: PD-L1 expression is an important negative prognostic factor in resected ADC. This finding has important implications for immunotherapy targeting the PD-1/PD-L1 pathway in patients with resected ADC.

KEYWORDS:

GSEA; lung adenocarcinoma; prognosis; programmed cell death-ligand 1

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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