The Prognostic and Clinicopathological Roles of PD-L1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Yan Li,Chen Yang,Shuyi Wei,Xiaohui Bian,Yaoyao Zhou,Lang Xie,Meizhi He,Odong Christopher

doi:10.3389/fphar.2019.00139

Yan Li, Chen Yang + Show 6 more

Open Access

https://doi.org/10.3389/fphar.2019.00139

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Abstract

Background: Studies evaluating the prognostic significance of programmed death-ligand 1 (PD-L1) expression in colorectal cancer (CRC) are limited and remain controversial. This meta-analysis was conducted in order to evaluate the clinicopathological and prognostic significance of PD-L1 expression in CRC patients.Methods: A comprehensive search was performed against the Medline/PubMed, Embase, Cochrane Library, Web of Science (WoS) and Scopus databases. Data were extracted with name of the first author, year of publication, country of origin, tumor type, number of cases, staining method, cut-off values, PD-L1 positive expression, clinicopathological parameters, outcome, and quality assessment score, and statistical analysis was conducted using Review Manager Version 5.3 (Revman the Cochrane Collaboration; Oxford, England) and STATA version 14 (Stata Corporation; College Station, TX, USA).Results: Ten studies were included in this meta-analysis, in which the pooled hazard ratio (HR) showed that PD-L1 expression in tumor cells was significantly associated with a poor overall survival (HR = 1.50, 95% CI 1.05–2.13, P = 0.03). The pooled HR for disease-free survival (DFS) indicated that PD-L1 expression was significantly associated with shorter DFS (HR = 2.57, 95% CI 1.40–4.75, P = 0.002). The pooled odds ratios (ORs) showed that PD-L1 expression was associated with poor differentiation (OR = 3.47, 95% CI 1.37–8.77, P = 0.008) and right colon cancer (OR = 2.38, 95% CI 1.57–3.60, P < 0.0001). However, the expression of PD-L1 was independent of gender, age, tumor size, tumor stage, lymph node metastasis, and tumor-node metastasis stage.Conclusion: This meta-analysis indicated that a high level of PD-L1 expression might be a biomarker for a poor prognosis in CRC patients. This information may be helpful for clinicians to stratify CRC patients for anti-PD-1/PD-L1 therapy, particularly patients with microsatellite instability high (MSI-H).

Highlights

Colorectal cancer (CRC) is the third leading cause of cancer (Siegel et al, 2017)
After exclusion of 626 duplicates, 3,356 articles about programmed death 1 (PD-1)/PDL1 in colorectal cancer were identified from a primary system literature search in the Medline/PubMed, Embase, Cochrane Library, wet of science (WoS), and Scopus databases
The pooled hazard ratio (HR) for disease-free survival (DFS) in tumor cells (TCs) with 452 patients indicated that programmed death-ligand 1 (PD-L1) expression was significantly associated with shorter DFS (HR = 2.57, 95%confidence intervals (CIs) 1.40–4.75, P = 0.002; see Figure 2C)

Summary

Introduction

Colorectal cancer (CRC) is the third leading cause of cancer (Siegel et al, 2017). As one of the most possible newly biomarkers to evaluate cancer patients’ outcomes, programmed death 1 (PD-1) is an immune-inhibitory receptor that is expressed on the surface of activated T cells as a result of persistent inflammatory stimuli (Inaguma et al, 2016; Zou et al, 2016). Studies evaluating the prognostic significance of programmed death-ligand 1 (PD-L1) expression in colorectal cancer (CRC) are limited and remain controversial. This meta-analysis was conducted in order to evaluate the clinicopathological and prognostic significance of PD-L1 expression in CRC patients

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Conclusion