The clinicopathological and prognostic significance of PD-L1 expression assessed by immunohistochemistry in lung cancer: a meta-analysis of 50 studies with 11,383 patients

Huijuan Li; Yangyang Xu; Bing Wan; Yong Song; Ping Zhan; Yangbo Hu; Qun Zhang; Fang Zhang; Hongbing Liu; Tianhong Li; Haruhiko Sugimura; Federico Cappuzzo; Dang Lin; Tangfeng Lv; written on behalf of AME Lung Cancer Collaborative Group

doi:10.21037/tlcr.2019.08.04

The clinicopathological and prognostic significance of PD-L1 expression assessed by immunohistochemistry in lung cancer: a meta-analysis of 50 studies with 11,383 patients

Transl Lung Cancer Res. 2019 Aug;8(4):429-449. doi: 10.21037/tlcr.2019.08.04.

Authors

Huijuan Li^{1

2}, Yangyang Xu³, Bing Wan⁴, Yong Song^{1

2

3}, Ping Zhan^{1

2}, Yangbo Hu⁵, Qun Zhang^{1

2}, Fang Zhang^{1

2}, Hongbing Liu^{1

2}, Tianhong Li⁶, Haruhiko Sugimura⁷, Federico Cappuzzo⁸, Dang Lin⁹, Tangfeng Lv^{1

2}; written on behalf of AME Lung Cancer Collaborative Group

Affiliations

¹ Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
² Nanjing University Institute of Respiratory Medicine, Nanjing 21000, China.
³ Department of Respiratory Medicine, Jinling Hospital, Nanjing Medical University, Nanjing 210002, China.
⁴ Department of Respiratory and Critical Care Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 210002, China.
⁵ Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, China.
⁶ Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis School of Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, California, USA.
⁷ Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
⁸ AUSL Romagna, Department of Oncology and Hematology, Ravenna, Italy.
⁹ Department of Respiratory and Critical Care Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China.

Abstract

Background: We conducted a meta-analysis to systematically evaluate the relationship between programmed death-ligand 1 (PD-L1) expression and survival in patients with lung cancer.

Methods: The electronic databases PubMed, Embase, Cochrane, and Web of Science were searched up to January 2^nd, 2018, for articles relating to PD-L1 expression detected by immunohistochemistry (IHC) and lung cancer patient prognosis.

Results: Fifty studies including 11,383 patients published between 2011 and 2017 were enrolled in this meta-analysis. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) suggested that PD-L1 IHC expression was related to poor overall survival (OS) (HR =1.45, 95% CI: 1.24-1.68). In subgroup analysis categorized according to sample type, cut-off value, ethnicity and TNM stage, the pooled results demonstrated inferior survival in the PD-L1 positive group when the PD-L1 expression was detected by resection specimens (P=0.000), 5% was taken as the cutoff value (P=0.000), the patients were in early stage (I-III) (P=0.000), and the geographic setting of the study was in Asia (P=0.000). Besides, patients with high PD-L1 expression had shorter OS in NSCLC (P=0.000), ADC (P=0.000), SCC (P=0.353) and LELC (P=0.810), while no significant difference was observed in SCLC (P=0.000). The pooled odds ratios (ORs) suggested that PD-L1 expression was associated with male (P<0.001), smoker (P<0.001), poor tumor differentiation (P=0.014), large tumor size (P=0.132), positive lymph nodal metastasis (P=0.002), EGFR wild-type status (P<0.001) and KRAS mutations (P=0.393). However, age (P=0.15) and ALK rearrangements (P=0.567) had no bearing on PD-L1 expression.

Conclusions: PD-L1 expression that is associated with several clinicopathological feactures may serve as a poor prognostic biomarker for patients with lung cancer.

Keywords: Lung cancer; meta-analysis; prognosis; programmed cell death ligand 1.