PD-1基因多态性与转移性食管鳞癌化疗敏感性及预后的关系

Relationship between PD-1 polymorphism and chemosensitivity and prognosis of metastatic esophageal squamous cell carcinoma

目的探讨程序性细胞死亡受体1(PD-1)单核苷酸多态性(SNP)与转移性食管鳞癌(ESCC)患者化疗疗效及预后的关系。方法对2013年1月至2018年3月在苏州科技城医院接受卡培他滨联合顺铂化疗的173例初治晚期转移性ESCC患者进行临床疗效评价,并随访无进展生存期(PFS)及总生存期(OS)。采用PCR-RFLP法对PD-1基因rs36084323 A/G、rs2227982 C/T及rs2227981 C/T多态性行基因型分析,采用χ2检验比较不同基因型对化疗疗效的影响,Kaplan-Meier法进行生存分析,采用Cox比例风险回归模型分析影响患者预后的因素。结果rs36084323位点A/G多态性与转移性ESCC化疗敏感性紧密相关,GG、AG、AA基因型患者的化疗有效率分别为23.7%、40.9%和48.1%,随着A等位基因的增加,化疗有效率明显提升。AA基因型的化疗有效率为GG基因型的2.984倍(95%CI:1.183~7.522,P=0.018),AG+AA基因型的化疗有效率是GG基因型的2.501倍(95%CI:1.100~5.688,P=0.026)。rs2227982 C/T多态性与患者的生存预后密切相关,随着T等位基因的增加,PFS及OS均逐渐延长,CC、CT、TT基因型患者的中位PFS分别为3.9、4.9和5.6个月(P=0.003),中位OS分别为8.6、12.3和13.7个月(P=0.018)。CT+TT基因型患者的中位PFS为5.1个月,与CC基因型的3.9个月比较差异有统计学意义(P=0.005)。同样,CT+TT基因型患者的中位OS为12.5个月,与CC基因型的8.6个月比较差异有统计学意义(P=0.020)。Cox多因素回归分析显示,rs2227982 C/T多态性是影响患者PFS和OS的独立预后因素。结论PD-1基因rs36084323 A/G多态性与转移性ESCC患者的化疗敏感性相关,rs2227982 C/T多态性可能影响患者的生存预后。

Objective To explore the relationship between single nucleotide polymorphism(SNP)of programmed death receptor 1(PD-1)and chemotherapy response and prognosis in patients with metastatic esophageal squamous cell carcinoma(ESCC).Methods From January 2013 to March 2018,173 patients with advanced metastatic ESCC who received capecitabine combined with cisplatin chemotherapy in Suzhou Science&Technology Town Hospital were evaluated for clinical efficacy,and the progression free survival(PFS)and overall survival(OS)were followed up.The polymorphisms of rs36084323 A/G,rs2227982 C/T and rs2227981 C/T of PD-1 gene were analyzed by PCR-RFLP.Chi square test was used to compare the effects of different genotypes on the response to chemotherapy,Kaplan Meier method was used for survival analysis,and Log-rank test was used for comparison between groups,Cox proportional hazards regression model was used to evaluate the influence of various factors on survival prognosis.Results Rs36084323 A/G polymorphism was closely related to the sensitivity of platinum chemotherapy in metastatic ESCC patients.The effective rates of chemotherapy in patients with GG,AG and AA genotypes were 23.7%,40.9%and 48.1%,respectively.With the increase of the number of A allele,the effective rate of chemotherapy was significantly increased.The effective rate of chemotherapy in AA genotype was 2.984 times higher than that of GG genotype(95%CI:1.183-7.522,P=0.018),and the effective rate of chemotherapy in patients with at least one A allele(AG+AA)was 2.501 times higher than that of GG genotype(95%CI:1.100-5.688,P=0.026).The rs2227982 C/T polymorphism was closely related to the prognosis of patients.With the increase of T allele number,PFS and OS were gradually extended.The median PFS of patients with CC,CT and TT genotype was 3.9,4.9 and 5.6 months(P=0.003),and the median OS was 8.6,12.3 and 13.7 months(P=0.018),respectively.The median PFS of patients with CT+TT genotype was 5.1 months,which was significantly different from 3.9 months of CC genotype(P=0.005).Similarly,the median OS of CT+TT genotype was 12.5 months,which was significantly longer than 8.6 months of CC genotype(P=0.020).Cox multivariate regression analysis showed that rs2227982 polymorphism was an independent prognostic factor for PFS and OS.Conclusion Rs36084323 A/G polymorphism is related to chemosensitivity in patients with metastatic ESCC,rs2227982 C/T polymorphism may affect the prognosis of patients.