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PD-L1 as a prognostic biomarker in surgically resectable non-small cell lung cancer: a meta-analysis.

ABSTRACT: Background:PD-L1 tumor expression has been associated with poor prognosis in a variety of solid tumors, including lung cancer, and represents a validated target for immune checkpoint inhibition in advanced malignances. It remains unknown, however, if PD-L1 can be used to predict survival in early stage, surgically treated cancers. This meta-analysis compares PD-L1 tumor expression and long term survival after surgical resection in early non-small cell lung cancer (NSCLC). Methods:PubMed was searched to identify eligible studies that compared survival of surgically resected stage I-III NSCLC patients according to PD-L1 tumor expression. Included studies were grouped according to measurement criteria of PD-L1 expression: 1%, 5%, 50% cutoffs or H-score. Meta-analysis was performed using a linear mixed-effects model to determine overall survival (OS). I2 was used as a measure of heterogeneity. Results:There were 40 eligible studies, including 10,380 patients. Regardless of cut-off used, higher PD-L1 tumor expression was associated with worse OS [hazard ratio (HR)1%: 1.59, 95% confidence interval (CI), 1.17-2.17; HR5%: 1.44, 95% CI, 1.03-2.00; HR50%: 1.52, 95% CI, 1.02-2.25, HRH-score: 1.34, 95% CI, 1.04-1.73]. Study heterogeneity was low and not statistically significant under all PD-L1 cutoffs. Conclusions:PD-L1 expression is consistently associated with worse survival, regardless of how it is quantified. In addition to acting as a prognostic biomarker, PD-L1 may also be used in future as a predictive biomarker for patients most likely to benefit from adjuvant immunotherapy.

SUBMITTER: Tuminello S

PROVIDER: S-EPMC7481631 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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PD-L1 as a prognostic biomarker in surgically resectable non-small cell lung cancer: a meta-analysis.

Tuminello Stephanie S Sikavi Daniel D Veluswamy Rajwanth R Gamarra Cesar C Lieberman-Cribbin Wil W Flores Raja R Taioli Emanuela E

Translational lung cancer research 20200801 4

<h4>Background</h4>PD-L1 tumor expression has been associated with poor prognosis in a variety of solid tumors, including lung cancer, and represents a validated target for immune checkpoint inhibition in advanced malignances. It remains unknown, however, if PD-L1 can be used to predict survival in early stage, surgically treated cancers. This meta-analysis compares PD-L1 tumor expression and long term survival after surgical resection in early non-small cell lung cancer (NSCLC).<h4>Methods</h4> ...[more]

PMID: 32953509

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Project description:BackgroundProgrammed cell death ligand-1 (PD-L1) and ligand-2 (PD-L2) interaction with programmed cell death protein-1 (PD-1) represent an immune-inhibiting checkpoint mediating immune evasion and is, accordingly, an important target for blockade-based immunotherapy in cancer. In non-small-cell lung cancer (NSCLC), improved understanding of PD-1 checkpoint blockade-responsive biology and identification of biomarkers for prediction of a clinical response to immunotherapy is warranted. Thus, in the present study, we systematically described PD-L1 and PD-L2 expression correlated genes in NSCLC.MethodsWe performed comparative retrospective analyses to identify PD-L1 and PD-L2 mRNA expression correlated genes in NSCLC. For this, we examined available datasets from the cancer cell line encyclopedia (CCLE) project lung non-small-cell (Lung_NSC) and the cancer genome atlas (TCGA) projects lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).ResultsAnalysis of the CCLE dataset Lung_NSC identified expression correlation between PD-L1 and PD-L2. Moreover, we identified expression correlation between 489 genes and PD-L1, 191 genes and PD-L2, and 111 genes for both. PD-L1 and PD-L2 also expression correlated in TCGA datasets LUAD and LUSC. In LUAD, we identified expression correlation between 257 genes and PD-L1, 914 genes and PD-L2, and 211 genes for both. In LUSC, we identified expression correlation between 26 genes and PD-L1, 326 genes and PD-L2, and 13 genes for both. Only a few genes expression correlated with PD-L1 and PD-L2 across the CCLE and TCGA datasets. Expression of Interferon signaling-involved genes converged in particular with the expression correlated genes for PD-L1 in Lung_NSC, for PD-L2 in LUSC, and for both PD-L1 and PD-L2 in LUAD. In LUSC, PD-L1, and to a lesser extent PD-L2, expression correlated with chromosome 9p24 localized genes, indicating a chromosome 9p24 topologically associated domain as an important driver of in particular LUSC PD-L1 expression. Expression correlation analyses of the PD-L1 and PD-L2 receptors programmed cell death protein-1 (PD-1), Cluster of differentiation 80 (CD80), and Repulsive guidance molecule B (RGMB) showed that PD-1 and CD80 expression correlated with both PD-L1 and PD-L2 in LUAD. CD80 expression correlated with PD-L2 in LUSC.ConclusionsWe present gene signatures associated with PD-L1 and PD-L2 mRNA expression in NSCLC which could possess importance in relation to understand PD-1 checkpoint blockade-responsive biology and development of gene signature based biomarkers for predicting clinical responses to immunotherapy.

Dataset Information

PD-L1 as a prognostic biomarker in surgically resectable non-small cell lung cancer: a meta-analysis.

Publications

PD-L1 as a prognostic biomarker in surgically resectable non-small cell lung cancer: a meta-analysis.

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