Lv Dan, Xing Chengjuan, Cao Lin, Zhuo Yuejian, Wu Tao, Gao Na
Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
Oncol Lett. 2020 Feb;19(2):1223-1234. doi: 10.3892/ol.2019.11221. Epub 2019 Dec 16.
Gastric cancer is one of the most prevalent malignant tumors worldwide. Immunological checkpoint inhibitors of the programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling pathway are effective in the treatment of various malignant tumor types, but the potential of such immunotherapeutic techniques for the treatment of gastric cancer is yet to be elucidated. The purpose of the present study was to investigate the methylation of the PD-L1 gene promoter and its clinical significance in advanced gastric cancer, as this may suggest the use of PD-L1 promoter methylation as a novel biomarker for gastric cancer progression. In a total of 70 samples, the methylation rate of the PD-L1 gene promoter region was significantly higher in gastric cancer tissues compared with adjacent tissues. A high level of PD-L1 promoter methylation was associated with lymph node staging, and resulted in poorer prognoses in patients with advanced gastric cancer. A total of 26 patients exhibited highly methylated PD-L1; in this group, the median progression-free survival time of patients receiving platinum/fluorouracil chemotherapy was 4.2 months longer than those receiving paclitaxel/fluorouracil chemotherapy, and the risk of disease progression in patients receiving paclitaxel/fluorouracil chemotherapy was 5.009 times higher compared with patients who received platinum/fluorouracil chemotherapy. Additionally, PD-L1 promoter methylation was significantly correlated with PD-L1 expression, and the progression of advanced gastric cancer. In conclusion, high methylation levels of the PD-L1 promoter region may be a faciliatory mechanism enabling gastric cancer tumorigenesis, and may also represent an independent prognostic factor for chemotherapeutic efficacy in patients with advanced gastric cancer.
胃癌是全球最常见的恶性肿瘤之一。程序性死亡1（PD-1）/程序性细胞死亡配体1（PD-L1）信号通路的免疫检查点抑制剂在治疗多种恶性肿瘤类型方面有效，但此类免疫治疗技术在胃癌治疗中的潜力尚待阐明。本研究的目的是探讨PD-L1基因启动子的甲基化及其在晚期胃癌中的临床意义，因为这可能提示将PD-L1启动子甲基化用作胃癌进展的新型生物标志物。在总共70个样本中，与癌旁组织相比，胃癌组织中PD-L1基因启动子区域的甲基化率显著更高。高水平的PD-L1启动子甲基化与淋巴结分期相关，并导致晚期胃癌患者的预后较差。共有26例患者的PD-L1高度甲基化；在该组中，接受铂/氟尿嘧啶化疗的患者的无进展生存期的中位数比接受紫杉醇/氟尿嘧啶化疗的患者长4.2个月，接受紫杉醇/氟尿嘧啶化疗的患者疾病进展的风险比接受铂/氟尿嘧啶化疗的患者高5.009倍。此外，PD-L1启动子甲基化与PD-L1表达及晚期胃癌的进展显著相关。总之，PD-L1启动子区域的高甲基化水平可能是促进胃癌发生的机制，也可能是晚期胃癌患者化疗疗效的独立预后因素。
