EB病毒相关性胃癌PD-1和PD-L1信号通路表达水平及意义

Expression levels of PD-1 and PD-L1 signaling pathways in patients with EB virus-associated gastric cancer and significance

目的探讨程序性细胞死亡蛋白-1(PD-1)、程序性细胞死亡蛋白-1配体(PD-L1)信号通路在EB病毒(EBV)相关性胃癌患者胃癌组织的表达。方法回顾性分析2017年6月-2021年6月在诸暨市中心医院消化内科就诊的190例胃癌患者,采用EB病毒编码的RNA(EBER)原位杂交法检测胃癌患者病理石蜡包埋组织中EBV表达情况,采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结(SP)法检测PD-1、PD-L1在胃癌组织中的表达。结果190例胃癌患者组织切片经EBER原位杂交方法检测出EBV阳性19例,阳性率为10.00%。肿瘤部位、浸润深度与EBV感染具有相关性(P<0.05)。190例胃癌组织中PD-1信号通路表达阳性例数为79例,阳性率为41.58%;PD-L1信号通路表达阳性例数为29例,阳性率为15.26%。EBV相关性胃癌与非EBV相关性胃癌患者胃癌组织中PD-1及PD-L1信号通路阳性表达率比较差异有统计学意义(P<0.05)。结论PD-1、PD-L1信号通路在EBV相关性胃癌中有较高的表达,对于近端胃及浸润深度较高的EBV感染高危胃癌患者,通过免疫检查点抑制治疗可能有更显著的治疗效果。

OBJECTIVE To explore the expression of programmed cell death protein-1(PD-1)and PD-1 ligand(PD-L1)signaling pathways in gastric cancer tissues of the patients with Epstein-Barr virus(EBV)-associated gastric cancer.METHODS Totally 190 gastric cancer patients who were treated in gastroenterology department of Zhuji Central Hospital from Jun 2017 to Jun 2021 were retrospectively analyzed.The expression of EBV in pathological paraffin-embedded tissues was detected by Epstein-Barr virus-encoded RNA(EBER)in situ hybridization method,and the expression levels of PD-1 and PD-L1 in gastric cancer tissues were detected by means of immunohistochemical streptavidin-perosidase(SP)method.RESULTS The result of EBER in situ hybridization for tissue sections showed that 19 cases were tested positive for EBV among the 190 gastric cancer patients,with the positive rate 10.0%.There was association between tumor site,invasion depth and EBV infection(P<0.05).Totally 79 cases were positive for expression of PD-1 signaling pathway in gastric cancer tissues of the 190 patients,with the positive rate 41.58%;totally 29 cases were tested positive for expression of PD-L1 signaling pathway,with the positive rate 15.26%.There were significant differences in the positive rates of expression of gastric tissue PD-1 and PD-L1 between the patients with EBV-associated gastric cancer and the patients with non-EBV-associated gastric cancer(P<0.05).CONCLUSION The patients with EBV-associated gastric cancer show high expression levels of PD-1 and PD-L1 signaling pathways.Immune checkpoint suppression therapy can achieve remarkable therapeutic effect on the gastric cancer patients with proximal stomach and high invasion depth at high risk of EBV infection.