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程序性死亡受体1基因多态性与胃癌铂类药物化疗敏感性的相关性研究

Correlation between programmed cell death-1 receptor gene polymorphism and sensitivity to platinum-based chemotherapy in gastric cancer

    摘要
  • 摘要:
      目的  探讨程序性死亡受体1（PD-1）基因rs36084323、rs2227982、rs7421861位点多态性与胃癌铂类药物化疗敏感性的相关性。
      方法  选取103例胃癌患者作为研究对象，给予奥沙利铂联合替吉奥（SOX）方案或者紫杉醇脂质体联合顺铂、5-氟尿嘧啶（PCF）方案化疗2个周期，化疗结束后根据实体肿瘤疗效评价标准（RECIST）1.1版将患者分为敏感组45例和抗拒组58例。化疗结束后，采集患者外周静脉血，应用TaqMan探针单核苷酸多态性（SNP）基因分型技术检测PD-1基因rs36084323、rs2227982、rs7421861位点多态性，并分析其与胃癌患者铂类药物化疗敏感性的关系。
      结果  PD-1基因rs36084323、rs2227982、rs7421861位点基因型频率分布均符合Hardy-Weinberg平衡定律（P>0.05）；敏感组与抗拒组的rs2227982、rs7421861位点PD-1基因型、等位基因分布情况比较，差异有统计学意义（P < 0.05）。rs2227982位点TT基因型（OR=1.739，95% CI为1.656~1.867）、CT基因型（OR=1.524，95% CI为1.435~1.663）化疗敏感性较CC基因型提高，T等位基因化疗敏感性较C等位基因提高（OR=1.721，95% CI为1.603~1.851），差异有统计学意义（P < 0.05）；rs7421861位点TT基因型（OR=1.605，95% CI为1.556~1.767）、CT基因型（OR=1.414，95% CI为1.372~1.525）化疗敏感性较CC基因型降低，T等位基因化疗敏感性较C等位基因降低（OR=1.531，95% CI为1.423~1.672），差异有统计学意义（P < 0.05）。Logistic回归分析结果显示，分化程度、PD-1基因rs2227982位点多态性、rs7421861位点多态性与胃癌患者铂类药物化疗敏感性显著相关（P < 0.01）。
      结论  PD-1基因rs2227982、rs7421861位点多态性可能与胃癌患者铂类药物化疗敏感性有关，rs2227982位点携带T等位基因者对铂类药物化疗反应性更好，rs7421861位点携带T等位基因者对铂类药物化疗反应性较差。

     

    Abstract:
      Objective  To investigate the correlations between rs36084323, rs2227982, rs7421861 polymorphisms of programmed cell death-1 receptor (PD-1) and sensitivity to platinum-based chemotherapy in gastric cancer.
      Methods  One hundred and three gastric cancer patients were selected as study objects, and given two cycles of oxaliplatin plus tiggio (SOX) or cisplatin, paclitaxel plus 5-fluorouracil (PCF) chemotherapy. After chemotherapy, the patients were divided into sensitive group (45 cases) and resistant group (58 cases) according to RECIST 1.1 version of solid tumor efficacy evaluation criteria(RECIST). After chemotherapy, peripheral venous blood was collected, and the polymorphism of rs36084323, rs2227982 and rs7421861 of PD-1 gene was detected by the TaqMan probe single nucleotide polymorphism (SNP) genotyping technique, and the relationship between the polymorphism and the susceptibility of patients with gastric cancer to platinum chemotherapy was analyzed.
      Results  The genotype frequency distribution of rs36084323, rs2227982 and rs7421861 of PD-1 gene complied with Hardy-Weinberg equilibrium law (P>0.05). The genotype and allele distribution of PD-1 locus rs2227982 and rs7421861 in the sensitive group and the resistant group showed significant differences(P < 0.05). The sensitive of TT genotype of allele T(OR=1.739, 95%CI, 1.656 to 1.867)and CT genotype(OR=1.524, 95%CI, 1.435 to 1.663)to chemotherapy and were significantly higher than that of CC genotype and C allele (P < 0.05). T allele had higher sensitivity to chemotherapy than C allele (OR=1.721, 95%CI, 1.603 to 1.851), and the difference was statistically significant (P < 0.05). TT genotype (OR=1.605, 95%CI, 1.556 to 1.767) and CT genotype (OR=1.414, 95%CI, 1.372 to 1.525) of rs7421861 had lower sensitivity to chemotherapy than CC genotype, and T allele had lower sensitivity to chemotherapy than C allele (OR=1.531, 95% CI, 1.423 to 1.672), and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that the degree of differentiation, rs2227982 polymorphism and rs7421861 polymorphism of PD-1 gene were significantly correlated with the sensitivity to platinum chemotherapy in gastric cancer patients (P < 0.01).
      Conclusion  The polymorphism of rs2227982 and rs7421861 locus of PD-1 gene may be related to the sensitivity of patients with gastric cancer to platinum chemotherapy, and the individuals carrying the T allele of rs2227982 have better response to platinum chemotherapy, and the individuals carrying the C allele of rs7421861 have poor response to platinum chemotherapy.

     

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