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

Research Paper

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

Jianli Ma1*, Decai Chi2*, Yan Wang3*, Yubo Yan3, Shu Zhao3, Hang Liu3, Jing Jing3, Haihong Pu3, Minghui Zhang3✉

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
*These authors contributed equally to this work

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Ma J, Chi D, Wang Y, Yan Y, Zhao S, Liu H, Jing J, Pu H, Zhang M. Prognostic value of PD-L1 expression in resected lung adenocarcinoma and potential molecular mechanisms. J Cancer 2018; 9(19):3489-3499. doi:10.7150/jca.26155. Available from http://www.jcancer.org/v09p3489.htm

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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: programmed cell death-ligand 1, lung adenocarcinoma, prognosis, GSEA