临床肿瘤学杂志

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PI3K/Akt相关基因多态性与胃癌含铂化疗方案疗效的关系分析

林秀欣,邓文静,余更生,吕华珠,李春鸣   

  1. 529030 广东江门 江门市中心医院肿瘤科
  • 收稿日期:2016-03-30 修回日期:2016-05-11 出版日期:2016-08-31 发布日期:2016-08-31

Analysis of the relationship between polymorphism of PI3K/Akt gene and efficacy of platinumbased chemotherapy for gastric cancer

LIN Xiuxin, DENG Wenjing, YU Gengsheng, LV Huazhu, LI Chunming   

  1. Department of Oncology,Jiangmen Central Hospital,Jiangmen 529030, China
  • Received:2016-03-30 Revised:2016-05-11 Online:2016-08-31 Published:2016-08-31

摘要: 目的 探讨PI3K/Akt信号通路中第10号染色体同源丢失性磷酸酶张力蛋白基因(PTEN)和磷脂酰肌醇激酶-3催化亚单位α(PIK3CA)的单核苷酸多态性(SNPs)与晚期胃癌含铂化疗方案疗效的关系。方法 采用Haploview 软件从国际人类基因组单体型图计划(Hap Map)公布的北京汉族人群基因型数据库中筛选出PTEN基因的4个标签SNPs(rs532678、rs926091、rs11202609、rs17431184)及PIK3CA基因的3个标签SNPs(rs2459693、rs3729679、rs12494623)。收集2012年1月至2015年12月158例晚期胃癌患者外周血标本并采用Sequenom MassArray质谱阵列技术对待检样本的以上7个SNPs进行基因分型;采用RECIST 11版标准评价以上患者接受含铂化疗方案2个周期的近期疗效,以CR+PR为敏感组、SD+PD为不敏感组,分析化疗敏感情况与以上SNPs位点基因型、等位基因的关系。结果 158例晚期胃癌患者PTEN及PIK3CA基因7个SNPs的基因型及等位基因分布均符合Hardy-Weinberg平衡。158例患者经2个周期化疗后共有化疗敏感者83例(CR 3例、PR 80例)和不敏感者75例(SD 42例、PD 33例)。PIK3CA rs3729679、rs12494623 SNPs与晚期胃癌含铂化疗方案的敏感性有关,其中携带突变等位基因者(rs3729679 G,rs12494623 T)的化疗敏感率较低,且化疗不敏感的风险显著升高,差异均有统计学意义(P<0.05);其余PIK3CA SNPs和PTEN SNPs位点基因分布与化疗敏感率及不敏感风险均无关(P>0.05)。结论 PIK3CA rs3729679、rs12494623 SNPs与晚期胃癌含铂方案化疗敏感性有关,且携带rs3729679 G或rs12494623 T等位基因者的化疗不敏感风险较高,对于预测晚期胃癌含铂化疗方案的疗效有一定价值。

Abstract: Objective To investigate the relationship of single nucleotide polymorphisms(SNPs)of phosphatase and tensin homolog deleted on chromosome ten(PTEN)and phosphatidylinositol 3-kinase catalytic alpha polypeptide(PIK3CA)of PI3K/Akt pathway with efficacy of platinum-based chemotherapy in patients with advanced gastric cancer. Methods Four tag SNPs of PTEN genes(rs532678,rs926091,rs11202609 and rs17431184)and 3 tag SNPs of PIK3CA genes(rs2459693,rs3729679 and rs12494623)from Beijing Han population database published by International HapMap Project(Hap Map)were screened using Haploview software.The peripheral blood samples of 158 patients from Jan 2012 to Dec 2015 with advanced gastric cancer were collected and MassArray mass spectrometry array was used to determine genotype. The short-term efficacy of platinum-based chemotherapy was evaluated by RECIST 1.1 creteria after two cycles of chemotherapy. Then the patients were assigned into sensitive group (CR+PR) and insensitive group(SD+PD). The relationship between sensitivity and above SNPs genotype/allele was analyzed. Results In 158 patients with advanced gastric cancer,the genotypes and the allele distribution of 7 SNPs in PTEN and PIK3CA genes were in line with the Hardy-Weinberg equilibrium. There were 83 patients in sensitive group(3 cases of CR and 80 cases of PR)and 75 patients in insensitive group(42 cases of SD and 33 cases of PD)after 2 cycles' chemotherapy. PIK3CA rs3729679 and rs12494623 SNPs were associated with the sensitivity of platinum-based chemotherapy in patients with advanced gastric cancer. Patients harboring mutation genes(rs3729679 G, rs12494623 T) had rather low sensitivity and an increased risk of insensitivity with the statistical significant differences(P<0.05). The remaining PIK3CA SNPs and PTEN SNPs loci were unrelated with sensitive rates and risk of insensitity(P>0.05). Conclusion PIK3CA rs3729679 and rs12494623 SNPs were associated with the sensitivity of platinumbased chemotherapy in patients with advanced gastric cancer. Patients harboring rs3729679 G or rs12494623 T are not sensitive to chemotherapy and have a higher risk for being insensitive to chemotherapy. It is helpful to predict the efficacy of platinum-based chemotherapy in patients with advanced gastric cancer.

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