PD-L1多态性与转移性食管鳞癌化疗敏感性及预后关系

Relationship Between PD-L1 Polymorphism and Chemosensitivity and Prognosis of Metastatic Esophageal Squamous Cell Carcinoma

目的探讨程序性细胞死亡配体-1(programmed cell death ligand-1,PD-L1)单核苷酸多态性(single nucleotide polymorphism,SNP)与转移性食管鳞癌(esophageal squamous cell carcinoma,ESCC)患者化疗反应及预后的关系。方法对2013年1月至2019年3月苏州科技城医院肿瘤科接受顺铂联合卡培他滨化疗的217例初治晚期转移性ESCC患者进行临床疗效评价,并随访总生存期(overall survival,OS)。采用PCR-RFLP法检测PD-L1基因rs4143815C/G、rs2297136T/C、rs10815225G/C多态性,用χ^(2)检验比较不同基因型间化疗反应的差异,Kaplan-Meier法进行生存分析,组间比较用Log-rank检验,Cox比例风险模型评估各种因素对生存预后的影响。结果 rs4143815C/G多态性与转移性ESCC化疗反应相关,随着G等位基因数目的增加,化疗有效率显著升高(CC 24.6%、CG 42.7%、GG 49.1%),CG基因型化疗有效率为CC基因型的2.29倍(95%CI 1.139-4.635,χ^(2)=5.466,P=0.019);GG基因型化疗有效率为CC基因型的2.98倍(95%CI 1.376-6.650,χ^(2)=7.371,P=0.007);CG+GG基因型化疗有效率为CC基因型的2.51倍(95%CI 1.307-4.712,χ^(2)=7.571,P=0.006)。Kaplan-Meier法及Log-rank检验显示,rs10815225G/C多态性与患者生存预后相关,随着C等位基因的增加,OS逐渐延长,GG、CG和CC基因型患者中位OS分别为8.7、13.5、14.3个月(χ^(2)=14.422,P=0.001),CG+CC基因型患者中位OS为13.6个月,与GG组比较差异有统计学意义(χ^(2)=9.983,P=0.002)。多因素分析结果显示,rs10815225G/C多态性仍是影响患者OS的独立预后因素。未发现rs2297136T/C多态性与化疗反应及预后之间存在统计学关联。结论 PD-L1基因rs4143815C/G多态性与转移性ESCC患者化疗敏感性相关,rs10815225G/C多态性可能影响患者生存预后。

Objective To explore relationship between single nucleotide polymorphism( SNP) of programmed cell death ligand-1( PD-L1) and chemotherapy response and prognosis in patients with metastatic esophageal squamous cell carcinoma( ESCC).Methods From January 2013 to March 2019,217 patients with advanced metastatic ESCC who received cisplatin combined with capecitabine chemotherapy in oncology department were evaluated for clinical efficacy,and overall survival( OS) were followed up.Polymorphisms of rs4143815 C/G、rs2297136 T/C and rs10815225 G/C of PD-L1 gene were analyzed by PCR-RFLP.Chi square test was used to compare different genotypes effects 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 risk model was used to evaluate influence of various factors on survival prognosis.Results Rs4143815 C/G polymorphism was associated with chemotherapy response of metastatic ESCC. With increase of G alleles number,effective chemotherapy rate was significantly increased( CC 24. 6%,CG42. 7%,GG 49. 1%).And response rate of CG genotype was 2. 29 times that of CC genotype( 95% CI 1. 139 - 4. 635,χ^(2) = 5. 466,P = 0. 019).Effective rate of GG genotype was 2. 98 times of CC genotype( 95% CI 1. 376 - 6. 650,χ^(2) = 7. 371,P = 0. 007).Effective rate of CG+GG genotype was 2. 51 times of CC genotype( 95% CI 1. 307 - 4. 712,χ^(2) = 7. 571,P = 0. 006).Kaplan Meier method and log rank test showed that rs10815225 G/C polymorphism was associated with survival and prognosis of patients. With C allele increase,OS was gradually prolonged.Median OS of GG,CG and CC genotypes were 8. 7,13. 5 and 14. 3 months,respectively( χ^(2)=14. 422,P = 0. 001).Median OS of CG+CC genotype patients was 13. 6 months,which was significantly different from that of GG group( χ^(2)= 9. 983,P = 0. 002).Multivariate analysis showed that rs10815225 G/C polymorphism was still an independent prognostic factor for OS.No significant correlation was found between rs2297136 T/C polymorphism and chemotherapy response and prognosis.Conclusion The rs4143815 C/G polymorphism of PD-L1 gene is associated with chemotherapy sensitivity in patients with metastatic ESCC,and rs10815225 G/C polymorphism may affect patients’ prognosis.