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张宇, 侯艳华, 张德志. TYMP基因多态性对结直肠癌患者R0切除术后辅助化疗疗效的影响[J]. 肿瘤防治研究, 2018, 45(7): 483-487. DOI: 10.3971/j.issn.1000-8578.2018.17.1667
引用本文: 张宇, 侯艳华, 张德志. TYMP基因多态性对结直肠癌患者R0切除术后辅助化疗疗效的影响[J]. 肿瘤防治研究, 2018, 45(7): 483-487. DOI: 10.3971/j.issn.1000-8578.2018.17.1667
ZHANG Yu, HOU Yanhua, ZHANG Dezhi. Influence of TYMP Polymorphism on Clinical Outcomes of Colorectal Cancer Patients Received Adjuvant Chemotherapy After R0 Resection[J]. Cancer Research on Prevention and Treatment, 2018, 45(7): 483-487. DOI: 10.3971/j.issn.1000-8578.2018.17.1667
Citation: ZHANG Yu, HOU Yanhua, ZHANG Dezhi. Influence of TYMP Polymorphism on Clinical Outcomes of Colorectal Cancer Patients Received Adjuvant Chemotherapy After R0 Resection[J]. Cancer Research on Prevention and Treatment, 2018, 45(7): 483-487. DOI: 10.3971/j.issn.1000-8578.2018.17.1667

TYMP基因多态性对结直肠癌患者R0切除术后辅助化疗疗效的影响

Influence of TYMP Polymorphism on Clinical Outcomes of Colorectal Cancer Patients Received Adjuvant Chemotherapy After R0 Resection

  • 摘要:
    目的 探讨胸苷磷酸化酶(thymidine phosphorylase, TYMP)基因变异是否对R0术后结直肠癌患者接受辅助化疗疗效有影响。
    方法 纳入198例术后接受辅助化疗的结直肠癌患者。收集患者外周血及术后癌组织标本分别用来进行TYMP基因5633C>T位点基因分型及TYMP基因表达测定。通过不同的分析方法分析该位点和其他变量的关系。Real-time PCR分析该位点不同基因型患者的TYMP mRNA表达水平。
    结果 TYMP基因5633C> T位点在CRC患者中的基因型分布频率为CC型126例(63.64%),CT型61例(30.81%),TT型11例(5.55%),最小等位基因频率为0.21,三种基因型分布频率符合哈迪温伯格平衡(P=0.323)。不同基因型患者基线资料均衡,预后分析上将CT/TT基因型合并。单变量生存分析结果显示:野生型的CC型患者OS较差,显著低于携带突变基因的CT型和TT型患者,差异有统计学意义(P=0.009)。多变量Cox模型校正之后发现CC基因型对OS有独立的影响(P=0.015)。另外,进一步在87例癌组织标本的mRNA表达分析中发现,突变的CT或TT型患者相对于野生型的CC型患者,癌组织中TYMP mRNA表达明显较高,差异有统计学意义(P=0.019)。
    结论 TYMP基因5633C>T位点可能通过影响TYMP mRNA的表达从而影响接受含卡培他滨辅助化疗方案的CRC患者的预后。

     

    Abstract:
    Objective To investigate the association between thymidine phosphorylase(TYMP) polymorphism and clinical outcomes of colorectal cancer(CRC) patients received adjuvant chemotherapy after R0 resection.
    Methods We included 198 patients with colorectal cancer who underwent adjuvant chemotherapy. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of 5633C > T and TYMP mRNA expression, respectively. The relationship between 5633C > T genotype and other variables was analyzed by different analysis methods. Additionally, the mRNA expression of TYMP according to 5633C > T were analyzed by real-time PCR.
    Results The prevalence of 5633C > T in TYMP among the CRC patients were as follows: 126(63.64%) cases of CC genotype, 61(30.81%) cases of CT genotype, 11(5.55%) cases of TT genotype, minimum allele frequency of 5633C > T was 0.21. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.323). There were no statistical differences in the distribution of the genotypes in baseline data. CT genotype and TT genotype patients were merged in the comparison of prognosis. The OS of patients with wild-type CC genotype was significantly lower than those with CT and TT genotypes (P=0.009). Adjusted in multivariate Cox regression analysis, CC genotype was an independent factor for OS (P=0.015). Additionally, of the 87 postoperative tissue specimens, the expression of TYMP mRNA in cancer tissues of the patients with CT or TT genotypes were significantly higher than those with wild-type CC genotype (P=0.019).
    Conclusion TYMP gene polymorphism 5633C > T may influence the prognosis of CRC patients who received capecitabine-based adjuvant chemotherapy by affecting the mRNA expression of TYMP.

     

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