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Prognostic value of PD-L1 in esophageal squamous cell carcinoma: a meta-analysis.

ABSTRACT: Accumulated evidence has shown that the programmed cell death receptor 1/programmed cell death receptor 1 ligand 1 (PD-1/PD-L1) pathway is a promising therapeutic target for cancer immunotherapy. However, the association between PD-L1 and esophageal squamous cell carcinoma (ESCC) patient survival remains unclear. We performed a meta-analysis to investigate the prognostic value of PD-L1 in ESCC. We searched PubMed, Embase, Web of Knowledge, and Cochrane Central Register of Controlled Trials databases for relevant studies that evaluated PD-L1 expression and ESCC patient survival. Fixed- and random-effects meta-analyses were conducted according to the heterogeneity of the included studies. Sensitivity analysis was performed according to Metan-based influence analysis. Publication bias was evaluated using Egger's and Begg's tests. Overall, 13 studies with 2,877 patients were included. Twelve studies demonstrated the association between overall survival (OS), and 6 studies described the relation between disease-free survival (DFS). PD-L1 overexpression was found in 43.7% (1,258 of 2,877) of the patients with ESCC. High PD-L1 expression was associated with distant metastasis in patients with ESCC (P = 0.04). Moreover, high PD-L1 expression was significantly associated with poor OS (hazard ratio [HR] 1.38, 95% confidence interval [CI] = 1.02-1.86, P = 0.04) and especially in Asian populations (HR 1.49, 95% CI = 1.11-1.99, P = 0.008). But it did not have an impact on disease-free survival (HR 1.15, 95% CI = 0.76-1.74, P = 0.52). Further well-designed clinical studies with uniform assessment approaches for PD-L1 expression are warranted to verify its prognostic value.

SUBMITTER: Guo W

PROVIDER: S-EPMC5862626 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Prognostic value of PD-L1 in esophageal squamous cell carcinoma: a meta-analysis.

Guo Wei W Wang Pan P Li Ning N Shao Fei F Zhang Hao H Yang Zhenlin Z Li Renda R Gao Yibo Y He Jie J

Oncotarget 20171227 17

Accumulated evidence has shown that the programmed cell death receptor 1/programmed cell death receptor 1 ligand 1 (PD-1/PD-L1) pathway is a promising therapeutic target for cancer immunotherapy. However, the association between PD-L1 and esophageal squamous cell carcinoma (ESCC) patient survival remains unclear. We performed a meta-analysis to investigate the prognostic value of PD-L1 in ESCC. We searched PubMed, Embase, Web of Knowledge, and Cochrane Central Register of Controlled Trials datab ...[more]

PMID: 29568405

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Project description:BackgroundImmunochemotherapy has become a new treatment for advanced esophageal squamous cell carcinoma (ESCC).AimsWe aimed to study the clinical efficacy and toxicity of immunochemotherapy based on PD-1/PD-L1 compared with chemotherapy alone in the treatment of advanced ESCC, focusing on analyzing the influence of PD-L1 expression level.Methods and resultsFive randomized controlled trials comparing PD-1/PD-L1 based immunochemotherapy with chemotherapy alone for advanced ESCC were included. We extracted efficacy data (objective response rate [ORR], disease control rate [DCR], overall survival [OS] rate, progression-free survival [PFS] rate) and safety data (treatment-related adverse events, treatment-related mortality) and performed meta-analyses. Compared with chemotherapy alone, the ORR and DCR of immunochemotherapy increased by 2.05 times and 1.54 times, respectively. Overall, patients receiving immunochemotherapy had a significant long-term survival advantage (OS: hazard ratio [HR] = 0.68, 95% confidence intervals [CI] 0.61-0.75; PFS: HR = 0.62, 95% CI 0.55, 0.70, respectively). Even with PD-L1 tumor proportion score <1%, immunochemotherapy also showed a significant survival advantage (OS: HR = 0.65, 95% CI 0.46-0.93; PFS: HR = 0.56, 95% CI 0.46-0.69, respectively). However, for PD-L1 combined positive score (CPS) < 1, the survival advantage of immunochemotherapy was not significant (OS: HR = 0.89, 95% CI 0.42-1.90; PFS: HR = 0.71, 95% CI 0.47-1.08, respectively). The toxicity of immunochemotherapy was higher than that of chemotherapy alone, but there was no statistical difference in treatment-related mortality (odds ratio = 1.11, 95% CI 0.67-1.83).ConclusionIn this study, treatment-related mortality was similar between immunochemotherapy and chemotherapy. PD-1/PD-L1 based immunochemotherapy significantly could improve survival outcomes in patients with advanced ESCC. For patients with CPS <1, the survival advantage of immunochemotherapy was not significant compared with chemotherapy.

Project description:BackgroundAbsent in melanoma 1-like (AIM1L), also known as crystalline beta gamma domain containing 2. The relationship between AIM1L and tumors has not been fully investigated, and the biological function of AIM1L in different tumors is unknown, so we bioinformatically explored a possible relationship between AIM1L and esophageal squamous cell carcinoma (ESCC).MethodsAIM1L mRNA expression was detected by the Gene Expression Omnibus database (GSE20347, GSE161533, and GSE53625), and protein level expression was detected by immunohistochemistry. The correlation between AIM1L expression and clinical pathological characteristics was evaluated by the Wilcoxon signed rank test or chi-square test. Kaplan-Meier analysis and Cox proportional risk regression model were used to determine the prognostic value of AIM1L in ESCC patients and establish and verify a nomogram. Find genes highly related to the expression of AIM1L, conduct GO and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and conduct GSEA analysis on the gene set. The "CIBERSORT" R package was used to explore the relationship between AIM1L and immune infiltration, and the "OncoPredict" R package was used to explore the relationship between AIM1L and drug sensitivity.ResultsCompared with the matched adjacent non-cancer tissues, the expression of AIM1L was down-regulated in ESCC tissues, and correlated with tumor grade. Kaplan-Meier survival analysis and Cox analysis showed that the low expression of AIM1L was related to the poor prognosis of ESCC patients. Enrichment analysis explained the possible function of AIM1L, GSEA determined the highly correlated signal pathway of AIM1L low expression phenotype, immune infiltration analysis determined that AIM1L was related to activated NK cells and macrophage M2, and drug sensitivity analysis determined that the low expression of AIM1L might be related to EGFR targeted drug resistance.ConclusionAIM1L may be a candidate tumor suppressor gene for ESCC and an independent molecular biomarker for the prognosis of ESCC patients.

Dataset Information

Prognostic value of PD-L1 in esophageal squamous cell carcinoma: a meta-analysis.

Publications

Prognostic value of PD-L1 in esophageal squamous cell carcinoma: a meta-analysis.

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