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PD-L1 is an independent prognostic predictor in gastric cancer of Western patients.

ABSTRACT: Targeting the PD-1/PD-L1 immune checkpoint signaling is a novel promising treatment strategy in several tumor entities, and it is suggested that PD-L1/PD-1 expression is predictive for a PD-1/PD-L1 checkpoint inhibitor treatment response. We investigated the expression of PD-L1 and PD-1 by immunohistochemistry in a large and well characterized gastric cancer (GC) cohort of Caucasian patients, consisting of 465 GC samples and 15 corresponding liver metastases. Staining results were correlated with clinico-pathological characteristics and survival. PD-L1 expression was found in tumor cells of 140 GCs (30.1%) and 9 liver metastases (60%) respectively in immune cells of 411 GCs (88.4%) and 11 liver metastases (73.3%). PD-1 was expressed in tumor infiltrating lymphocytes in 250 GCs (53.8%) and in 11 liver metastases (73.3%). PD-L1 expression was significantly more prevalent in men, GCs of the proximal stomach, unclassified, papillary, Her2/neu-positive, Epstein-Barr-virus-positive, microsatellite instable, and PIK3CA-mutated GCs. A high PD-L1/PD-1 expression was associated with a significantly better patient outcome, and PD-L1 turned out to be an independent survival prognosticator. The correlation of PD-L1/PD-1 expression with distinct clinico-pathological patient characteristics may serve as a surrogate marker of PD-L1-positive GCs and may direct the use of immune checkpoint treatment strategies.

SUBMITTER: Boger C

PROVIDER: S-EPMC5029700 | biostudies-other | 2016 Apr

REPOSITORIES: biostudies-other

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PD-L1 is an independent prognostic predictor in gastric cancer of Western patients.

Böger Christine C Behrens Hans-Michael HM Mathiak Micaela M Krüger Sandra S Kalthoff Holger H Röcken Christoph C

Oncotarget 20160401 17

Targeting the PD-1/PD-L1 immune checkpoint signaling is a novel promising treatment strategy in several tumor entities, and it is suggested that PD-L1/PD-1 expression is predictive for a PD-1/PD-L1 checkpoint inhibitor treatment response. We investigated the expression of PD-L1 and PD-1 by immunohistochemistry in a large and well characterized gastric cancer (GC) cohort of Caucasian patients, consisting of 465 GC samples and 15 corresponding liver metastases. Staining results were correlated wit ...[more]

PMID: 27009855

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Project description:BackgroundThe CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is a key regulator of the programed death receptor ligand-1 (PD-L1) protein. However, the usefulness of CMTM6 expression as a prognostic indicator and the relationship between CMTM6 and PD-L1 expression in gastric cancer (GC) remains unclear.ObjectivesWe evaluated the expression and prognostic implications of CMTM6 in GC tissue and its relationship with PD-L1 expression.Patients and methodsThe protein expressions of CMTM6 and PD-L1 were detected in 122 cases of postoperative GC tissue using immunohistochemical (IHC) assays. Kaplan-Meier survival analysis was used to calculate the survival probability and a log-rank test was used to compare the survival curves. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the clinically-related factors associated with survival. Pearson's correlation was used to determine the correlation analysis and estimate the statistical significance. The univariate and multivariate logistic regression analyses were used to analyze the relationship between clinically-related factors and PD-L1 expression.ResultsKaplan-Meier survival analysis showed that patients with high CMTM6 expression had shorter overall survival (OS) than those with low expression (P < 0.001). The expression of CMTM6 was an independent risk factor for prognosis in multivariate Cox proportional hazard regression analyses (HR:2.221, CI% [1.36-3.628], P = 0.001). The OS of patients with positively expressed PD-L1 was significantly shorter than those with negatively expressed PD-L1 (P = 0.003). The expression of CMTM6 was significantly related to the positive expression of PD-L1 in gastric cancer tissues (r = 0.186, P = 0.041). The expression of CMTM6 was the independent risk factor for PD-L1 expression in multivariate logistic regression analysis (OR:2.538, CI% [1.128-5.714], P = 0.024).ConclusionCMTM6 expression is significantly related to PD-L1 and may be a useful prognostic indicator and a specific therapeutic target for cancer immunotherapy for GC patients.

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PD-L1 is an independent prognostic predictor in gastric cancer of Western patients.

Publications

PD-L1 is an independent prognostic predictor in gastric cancer of Western patients.

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