Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection

Eto, Shohei; Yoshikawa, Kozo; Nishi, Masaaki; Higashijima, Jun; Tokunaga, Takuya; Nakao, Toshihiro; Kashihara, Hideya; Takasu, Chie; Iwata, Takashi; Shimada, Mitsuo

doi:10.1007/s10120-015-0519-7

Cited by 133 publications

(151 citation statements)

References 25 publications

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“…However, for patients with GC, the association between the expression of PD-L1 and their prognosis remains controversial. Multiple studies have indicated that positive PD-L1 expression is associated with a significantly poor OS1617181920212223, but other studies could not confirm this finding2425.…”

Section: Discussionmentioning

confidence: 99%

The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients

Zhang

Dong

Liu

et al. 2016

Sci Rep

120

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The prognostic value of programmed death-ligand 1 (PD-L1) in gastric cancer (GC) remains controversial. To clarify this problem, we performed a meta-analysis of research studies identified in the PubMed, EMBASE and the Cochrane Library databases. A total of 1,901 patients in 10 studies were enrolled in this meta-analysis, and the pooled hazard ratio (HR) of 1.64 (95% CI 1.11 to 2.43; P = 0.01) indicated that PD-L1 expression is associated with a shorter overall survival (OS). The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with tumour size (OR = 1.87, 95% CI 1.25 to 2.78; P = 0.002) and lymph node status (OR = 2.17, 95% CI 1.04 to 4.52; P = 0.04). However, PD-L1 had no correlation with gender, age, cancer location, differentiation, depth of invasion, and tumour stage. This meta-analysis indicates that PD-L1 expression is a valuable predictor of the prognosis of patients with GC. PD-L1 expression could be used for identifying a subgroup of patients, who would potentially benefit from targeted therapy against PD-1 or PD-L1. Well-designed large-cohort studies are needed to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients

Zhang

Dong

Liu

et al. 2016

Sci Rep

120

View full text Add to dashboard Cite

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“…Multiple studies on gastric carcinoma utilizing immunohistochemistry (IHC) for PD-L1 demonstrated varying rates of PD-L1 expression, ranging from 5.1% to 65.0% [16–26]. In the majority of studies, PD-L1 expression was associated with an unfavorable prognosis [16–22, 25, 26]; however, recent studies have linked PD-L1 expression with a favorable prognosis [23, 24]. …”

Section: Introductionmentioning

confidence: 99%

Programmed cell death-ligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability

et al. 2017

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Programmed death-ligand 1 (PD-L1) is expressed in a subgroup of gastric cancers that may benefit from immunotherapy. Microsatellite instability-high (MSI-H) is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1. The relationship between PD-L1 expression and MSI-H status remains poorly understood. In this study, we investigated PD-L1 expression in patients with MSI-H gastric cancer. We analyzed PD-L1 expression in 78 MSI-H gastric cancer tissue samples using immunohistochemistry. PD-L1 expression was classified as expression on tumor cells or on immune cells. We observed PD-L1 expression in 48 gastric cancer samples (61.5%), consisting of 7 (9.0%) cases with tumor PD-L1 expression and 47 (60.3%) cases with immune cell PD-L1 expression. Immune cell PD-L1 expression was frequently associated with intestinal type cancer by the Lauren classification (p = 0.015), with a lower risk of lymph node metastasis (p = 0.027) and lower tumor stages (p = 0.029) compared to MSI-H gastric cancers without PD-L1 expression. Moreover, immune cell PD-L1 expression was an independent favorable prognostic factor for overall survival (versus PD-L1 negative; hazard ratio, 3.451; 95% confidence interval, 1.172–12.745; p = 0.025). In MSI-H gastric cancer, PD-L1 expression was observed to be independently associated with a longer survival.

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“…Since it is difficult to get fresh specimens from patients to determine the expression of PD-1 or PD-L1 expression by IHC, no uniform standard was defined for PD-L1 positivity up to now. Eto et al defined PD-L1 positivity by staining of the tumor-cell in four grade: 6–25, 26–50 or 51–75 and 76–100% of cells (12,23–29); Ti Wen and co-worker defined staining pattern of PD-L1 as positive if <5 or ≥5% in tumor cells (13); whereas Wenfeng Fang assessed the expression of PD-L1 by semi-quantitative H-score and defined cases with greater than 10% PD-L1 expression on tumor cells were considered positive (26). Therefore, consistency detection of PD-1 and PD-L1 expression by IHC is limited due to the difference of antibody qualities from different manufacturers, the interpretative subjectivity, and the different standard on positivity thresholds.…”

Section: Discussionmentioning

confidence: 99%

“…The inclusion criteria were listed as follows: i) The diagnosis of metastatic gastric cancer was confirmed by endoscopic biopsy and imageological examination; ii) the disease was classified as pathologic M1 with any T and N stage based on the standard of the WHO Classification of Tumors of the Digestive System, 2010 edition (12,13); iii) 2 ml peripheral blood was drawn before the first line therapy; iv) patients had completed 4 courses of first line chemotherapy as documented in the medical record; and v) complete follow-up data was available. This study was approved by the ethics committee at the Zhengzhou University Affiliated Cancer Hospital, and informed consent form was signed by every patient.…”

Section: Methodsmentioning

confidence: 99%

High expression of programmed cell death protein 1 on peripheral blood T‑cell subsets is associated with poor prognosis in metastatic gastric cancer

Shi

et al. 2018

Oncol Lett

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Immune checkpoints in solid tumors serve important roles in metastasis. The present study was designed to explore the expression of programmed cell death protein 1 (PD-1) on peripheral blood T-cell subsets and its role in the clinicopathological features and prognosis of patients with metastatic gastric cancer. The expression of PD-1 in peripheral blood T-cell subsets was detected in 100 metastatic gastric cancer patients prior to the first line chemotherapy by flow cytometric analysis. The potential associaton between the peripheral blood T-cell subsets PD-1 level and the clinicopathological features of patients with metastatic gastric cancer and the clinical outcomes was analyzed. The percent of high PD-1 expressed cluster of differentiation (CD)3+, CD3+CD4+ and CD3+CD8+ T-cells was 20.4, 13.0 and 9.4%, respectively in patients with metastatic gastric cancer. The overall survival (OS) and progression-free survival (PFS) rate of the 100 patients with metastatic gastric cancer was 12.2 and 3.9 months, respectively. Kaplan-Meier curve with long-rank analysis indicated that patients with higher PD-1+/CD3+, PD-1+/CD3+CD4+ and PD-1+/CD3+CD8+ levels had a worse prognosis (all P<0.05). Univariate and multivariate analysis revealed that high PD-1+/CD3+ [hazard ratio (HR), 2.145; P=0.015], high PD-1+/CD3+CD4+ (HR, 1.866; P=0.034) and high PD-1+/CD3+CD8+ (HR, 1.817; P=0.033) level in peripheral blood were independent risk factors for predicting the survival time of patients with metastatic gastric cancer. High PD-1+/CD3+, high PD-1+/CD3+CD4+ and high PD-1+/CD3+CD8+ expression conferred a lower overall survival rate in patients with metastatic gastric cancer. These results suggest that high PD-1 expression on peripheral blood T-cell subsets may potentially be novel prognostic biomarker for metastatic gastric cancer.

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Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection

Abstract: PD-1 expression is associated with a poor prognosis and is correlated with PD-L1 and Foxp3 expression in patients with gastric cancer.

Cited by 133 publications

References 25 publications

The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients

The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients

Programmed cell death-ligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability

High expression of programmed cell death protein 1 on peripheral blood T‑cell subsets is associated with poor prognosis in metastatic gastric cancer

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