Du Zixuan, Yan Derui, Li Zhongyang, Gu Jincheng, Tian Ye, Cao Jianping, Tang Zaixiang
Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China.
J Oncol. 2020 Sep 8;2020:7314195. doi: 10.1155/2020/7314195. eCollection 2020.
The PD-1/PD-L1 pathway plays an important role in the treatment of cancers as immune checkpoint. However, the association of genes involved in the PD-L1 pathway and radiosensitivity of gastric cancer has not been fully characterized. This study aims to explore the relationship between the expression levels of genes involved in the PD-L1 pathway and radiosensitivity for gastric cancer patients. A total of 367 patients with clinical survival information and radiotherapy information were obtained in The Cancer Genome Atlas (TCGA). Genes involved in the PD-L1 pathway were categorized into high and low expression level groups according to the median value. The Cox proportional hazards model was used to find the association between gene expression level and radiosensitivity. The results show that high expression levels of CD274, EGFR, RAF1, RPS6KB1, PIK3CA, MTOR, CHUK, NFKB1, TRAF6, FOS, NFATC1, and HIF1A were associated with radiosensitivity of gastric cancer. While low expression level of HRAS was also associated with radiosensitivity in gastric cancer. The rates of a new tumor event and disease progression were lower for radiosensitivity patients than other patients. The relationship between the expression level of CD274 and other genes involved in the PD-L1 pathway is significant. GO (Gene Ontology) analysis shows that the biological process of 13 genes was mainly related to innate immune response activating the cell surface receptor signaling pathway. KEGG analysis demonstrated that 13 genes in gastric cancer are mainly related to the PD-L1 expression and PD-1 checkpoint pathway in cancer. The correlation between the expression level of CD274 and other genes involved in the PD-L1 pathway is significant. The present study offered more evidence for using PD-L1 and genes involved in the PD-L1 pathway as potential biomarkers to predict radiosensitive patients with gastric cancer.
PD-1/PD-L1通路作为免疫检查点在癌症治疗中发挥着重要作用。然而,PD-L1通路相关基因与胃癌放射敏感性之间的关联尚未完全明确。本研究旨在探讨PD-L1通路相关基因的表达水平与胃癌患者放射敏感性之间的关系。在癌症基因组图谱(TCGA)中获取了367例具有临床生存信息和放疗信息的患者。根据中位数将PD-L1通路相关基因分为高表达水平组和低表达水平组。采用Cox比例风险模型来寻找基因表达水平与放射敏感性之间的关联。结果显示,CD274、EGFR、RAF1、RPS6KB1、PIK3CA、MTOR、CHUK、NFKB1、TRAF6、FOS、NFATC1和HIF1A的高表达水平与胃癌的放射敏感性相关。而HRAS的低表达水平也与胃癌的放射敏感性相关。放射敏感患者的新肿瘤事件和疾病进展发生率低于其他患者。CD274的表达水平与PD-L1通路中的其他基因之间的关系显著。基因本体论(GO)分析表明,13个基因的生物学过程主要与激活细胞表面受体信号通路的先天免疫反应相关。京都基因与基因组百科全书(KEGG)分析表明,胃癌中的13个基因主要与癌症中的PD-L1表达和PD-1检查点通路相关。CD274的表达水平与PD-L1通路中的其他基因之间的关系显著。本研究为将PD-L1及PD-L1通路相关基因作为预测胃癌放射敏感患者的潜在生物标志物提供了更多证据。