title: Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance.
abstract: 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.
authors.affiliation: Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Advanced Cell Diagnostics, Inc., Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Advanced Cell Diagnostics, Inc., Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D012333:RNA, Messenger; D012313:RNA
keywords: RNA in situ hybridization; advanced gastric cancer; immunohistochemistry; programmed death-ligand-1