基于癌组织KDM3A表达分析信迪利单抗联合DOS方案治疗晚期胃癌的机制

The mechanism of sindilizumab combined with DOS regimen in the treatment of advanced gastric cancer based on KDM3A expression in cancer tissues

目的 研究信迪利单抗联合多西他赛+奥沙利铂+替吉奥(DOS)方案对晚期胃癌患者癌组织赖氨酸去甲基化酶3A(KDM3A)表达的影响及治疗机制。方法 选择2019年6月至2021年6月收治的104例晚期胃癌患者,随机分为对照组和观察组,每组52例。对照组患者行DOS方案治疗,观察组在对照组基础上加用信迪利单抗。比较2组患者治疗前后肿瘤标志物[癌胚抗原(CEA)、糖类抗原724(CA724)、糖类抗原125(CA125)]、肿瘤免疫分子(CD9、CD63、CD168、CD151)水平、癌组织程序性死亡受体-1(PD-1)/及其配体PD-L1、KDM3A阳性表达率,并做Karnofsky功能状态(KPS)评分,评价临床疗效、不良反应及生存预后。结果 治疗后与对照组比较,观察组CEA、CA724、CA125均降低(P<0.05)。治疗后与对照组比较,观察组CD168、CD151均降低,CD9、CD63均升高(P<0.05)。治疗后与对照组比较,观察组PD-1、PD-L1、KDM3A阳性率均降低(P<0.05)。治疗后与对照组比较,观察组KPS评分均升高(P<0.05)。与对照组比较,观察组客观有效率、疾病控制率均升高(P<0.05)。2组不良反应比较差异无统计学意义(P>0.05)。与对照组比较,观察组中位生存期延长,12个月、24个月生存率升高(P<0.05)。结论 信迪利单抗联合DOS方案可抑制晚期胃癌患者肿瘤标志物分泌,延长生存周期,其机制可能与抑制PD-1/PD-L1信号转导、提高机体免疫力、降低KDM3A活性、抑制肿瘤细胞增殖与迁移有关。

Objective To investigate the effect of sindilizumab combined with docetaxel+oxaliplatin+S-1(DOS)regimen on the expression of lysine demethylase 3A(KDM3A)in advanced gastric cancer tissues and its therapeutic mechanism.Methods A total of 104 patients with advanced gastric cancer admitted to our hospital from June 2019 to June 2021 were divided into the control group(n=52)and observation group(n=52).The DOS regimen was applied to both groups,and patients in the observation group were additionally treated with sindilizumab.Tumor markers,including carcinoembryonic antigen(CEA),carbohydrate antigen 724(CA724)and carbohydrate sugar antigen 125(CA125);tumor immune molecules before treatment(CD9,CD63,CD168,CD151);positive expressions of programmed death receptor-1(PD-1),PD-L1 and KDM3A;the Karnofsky functional status(KPS)score;adverse effects;survival and prognosis were compared between groups.Results After treatment,CEA,CA724 and CA125 in observation group were significantly lower compared with those of control group(P<0.05).After treatment,CD168 and CD151 were significantly lower,while CD9 and CD63 were significantly higher in observation group compared with those of control group(P<0.05).After treatment,the positive rates of PD-1,PD-L1 and KDM3A in the observation group were significantly lower compared with those of control group(P<0.05).After treatment,KPS score of observation group was significantly higher compared with that of control group(P<0.05).Compared with those of control group,the objective effective rate and disease control rate of observation group were significantly higher(P<0.05).There was no significant difference in the incidence adverse events between the two groups(P>0.05).Compared with those of the control group,the median survival time,12-month and 24-month survival rate of observation group were significantly longer(P<0.05).Conclusion Sindilizumab combined with DOS regimen can inhibit the secretion of tumor markers in patients with advanced gastric cancer and prolong the lifespan by inhibiting the PD-1/PD-L1 signal transduction,improving body immunity,reducing KDM3A activity,and suppressing tumor cell proliferation and migration.