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目的:探讨EDN1及EDNRA基因多态性与初治局部区域晚期鼻咽癌患者预后的关系。方法:采用LDR-PCR技术对203例鼻咽癌患者EDN1及EDNRA基因7个位点的基因多态性(SNP)进行检测,用Kaplan-Meier法进行生存分析,多因素分析采用Cox回归模型。结果:携带EDN-RA/H323H突变型杂合子TC基因型患者的5年无进展生存率(PFS)、总生存率(OS)、无远处转移生存率(DMFS)及无局部区域复发生存率均比携带纯合子CC+TT基因型的患者低,P<0.05;Cox模型多因素分析显示,EDNRA/H323HSNPs是影响局部晚期鼻咽癌患者PFS(HR:1.964;P=0.004)、OS(HR:1.955;P=0.009)、DMFS(HR:1.984;P=0.023)及LRFS(HR:2.112;P=0.036)的独立预后因素。携带EDNRA/G-231A突变基因型GA或AA患者的5年PFS和LRFS均低于携带野生型GG基因型患者(P<0.05),Cox模型多因素分析显示,EDNRA/G-231ASNPs是影响局部晚期鼻咽癌患者PFS(HR:1.826;P=0.017)及LRFS(HR:3.262;P=0.005)的独立预后因素。结论:EDNRA基因H323H、G-231ASNPs是影响局部区域晚期鼻咽癌的独立预后因素,为晚期鼻咽癌的预后判断及个体化治疗提供了新的分子指标。
Objective: To investigate the relationship between the polymorphisms of EDN1 and EDNRA and the prognosis of patients with locally advanced nasopharyngeal carcinoma. Methods: The SNPs of EDN1 and EDNRA genes in 203 NPC patients were detected by LDR-PCR. Survival analysis was performed by Kaplan-Meier method and Cox regression model was used for multivariate analysis. RESULTS: The 5-year progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and local recurrence-free survival in patients with the TC genotype of the EDN-RA / H323H mutant heterozygote P <0.05). Cox model multivariate analysis showed that EDNRA / H323HSNPs were significantly associated with PFS (HR: 1.964; P = 0.004), OS : 1.955; P = 0.009), DMFS (HR: 1.984; P = 0.023) and LRFS (HR: 2.112; P = 0.036). The 5-year PFS and LRFS of patients with genotype GA or AA with EDNRA / G-231A mutation were lower than those with wild-type GG genotype (P <0.05). Multivariate analysis of Cox model showed that EDNRA / G-231ASNPs affected local The independent prognostic factors of PFS (HR: 1.826; P = 0.017) and LRFS (HR: 3.262; P = 0.005) in patients with advanced nasopharyngeal carcinoma. Conclusion: The EDNRA genes H323H and G-231ASNPs are independent prognostic factors of advanced nasopharyngeal carcinoma in the local area and provide new molecular markers for the prognosis and individualized treatment of advanced nasopharyngeal carcinoma.