Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric&amp;nbsp;cancer

Qu, Yi; Li, Qing; Ren, Tao; Xia, Wei; Peng, Yu; Liu, Gao lei; Luo, Hao; Yang, Yue; Dai, Xiaohui; Zhou, Shu‐Feng; Wang, Dong

doi:10.2147/dddt.s75152

Cited by 158 publications

(133 citation statements)

References 45 publications

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“…PD-L1 expression has been associated with clinicopathological characteristics and prognosis in different cancers [21–24]. We found no significant difference between PD-L1 mRNA expression and gender, age, KPS score, differentiation, the number of metastatic organs, liver metastasis, and peritoneal metastasis ( P > 0.05).…”

Section: Discussionmentioning

confidence: 51%

Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance

et al. 2016

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PD-L1 expression may be a predictive marker for anti-PD-1 therapeutic efficacy. No standard detection method of PD-L1 expression was available for advanced gastric cancer (AGC), which would be investigated in this study using RNA in situ hybridization and immunohistochemistry. Patients (N = 165) with AGC treated at Peking University Cancer Hospital from October 2008 to February 2013 were retrospectively studied. Tissue samples prior to chemotherapy were assessed for PD-L1 expression using RNA in situ hybridization (an RNAscope assay) and immunohistochemistry (IHC). The correlations of PD-L1 expression to patient characteristics and clinical outcomes were statistically analyzed. PD-L1 mRNA signals were located in tumor compartments or the mesenchyme in a brown dotted or clustered pattern, and PD-L1 mRNA expression in gastric cancer was heterogeneous. PD-L1-positive expressions were observed in 33.9% (56/165) and 35.1% (46/131) patients in mRNA level and protein level, respectively. A positive relationship was found between PD-L1 mRNA and PD-L1 protein, and compared to IHC, RNAscope assay could provide an intuitional and quantitative data with potential clinical application. No statistically significant differences occurred between PD-L1 expression and clinical response to chemotherapy, or survival. However, we found that PD-L1 expression was higher in intestinal type than in diffuse type. These findings suggested that the RNAscope assay may be a promising method for patient assessment in gastric cancer clinical trials, which would be illustrated in further study.

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Section: Discussionmentioning

confidence: 51%

Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance

et al. 2016

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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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“…In an unselected GC population, PD-L1 was overexpressed in 42%-50% of patients (52) (53) , and was correlated with poor survival rates (53) . Inhibition of PD-L1…”

Section: Pd-1/pd-l1 Pd-l2 Pathwaymentioning

confidence: 99%

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Jácome

Lima

Kazzi

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancerrelated mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

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Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer

Cited by 158 publications

References 45 publications

Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance

Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance

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

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

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