目的 探讨线粒体D-环区(D-loop区)单核苷酸多态性与食管癌患者预后的关系.方法 选择2003-2004年在河北医科大学第四医院胸外科住院行食管癌根治性手术切除的食管癌患者55例,采用聚合酶链反应对其手术切除标本进行线粒体D-loop区测序.通过电话对患者进行随访并计算5年生存率,分析其与患者临床特征的关系.参照基因数据库AC_000021号从已完成的食管癌患者线粒体D-loop区1 000 bp序列中找出单核苷酸多态性位点,分析不同单核苷酸多态性位点与患者5年生存率的关系.结果 本组55例患者均完成了5年的随访,共生存20例.不同性别、年龄(以55岁为界)及有无淋巴结转移食管癌患者5年生存率比较,差异均无统计学意义(P＞0.05);不同TNM分期食管癌患者5年生存率比较,差异有统计学意义(P＜0.05).共找出88个单核苷酸多态性位点,采用Kaplan-Meier方法绘制生存曲线发现,仅16278和16399位点与食管癌患者的生存期有关.16278T型食管癌患者与16278C型患者、16399G型食管癌患者与16399A型患者5年生存率比较,差异均有统计学意义(χ2值分别为9.413和11.225,P＜0.05).采用Cox比例风险回归模型分析发现,16278T/C[OR=3.638,95%CI(1.191,11.111)]和16399G/A[OR=5.096,95%CI(1.647,15.769)]是食管癌患者预后的独立预测因子(P＜0.05).结论 线粒体D-loop区单核苷酸多态性可作为食管癌患者预后的预测因子,有助于早期判断食管癌患者预后,更好地指导临床治疗,对估计生存期较短的术后患者可给予更积极的辅助治疗,以提高患者生存率.%Objective To study the relationship between single nucleotide polymorphisms ( SNPs ) in mitochondrial DNA ( mtDNA ) displacement - loop ( D - loop ) region and prognosis of patients with esophageal squamous cell carcinoma ( ESCC ) . Methods 55 ESCC patients underwent radical operation in department of thoracic surgery of the Fourth Hospital of Hebei Medical University from 2003 to 2004 were selected. The D - loop region of mtDNA was sequenced by using polymerase chain reaction method. The patients were followed up by telephone for five years, and then the five year survival rate was calculated and its relationship with clinical features was analyzed. AC_ 000021 database was referred to in order to find SNPs from the 1 000 - bp mitochondria D - Loop region, and the relationship between SNPs and five year survival rate was analyzed. Results All the 55 patients completed the five - year following up and 20 cases survived. The survival rate between patients with different sex, age ( 55 as dividing line ) and whether there was lymphatic metastasis or not showed no statistically significant differences ( P > 0. 05 ) . The five - year survival rate between patients with different TNM staging showed statistically significant difference ( P <0. 05 ) .88 SNPs sites were detected in the 1 000 - bp mitochondria D - Loop region. When drawing the survival curves with Kaplan - Meier method, only SNP sites of nucleotides 16278C/T and 16399A/G showed correlation with the survival of patients. The five -year survival rate between patients with 16278T and 16278C and patients with 16399G and 16399A both showed statistically significant differences ( x =9. 413 and 11. 225 , P <0. 05 ) . Cox proportional hazards regression models showed that 16278T/C [OR=3. 638, 95%CI (1.191, 11.111)] and 16399G/A [ OR =5. 096, 95%CI (1.647, 15.769)] were independent risk factors for the prognosis of ESCC patients. Conclusion SNPs in the D - loop are independent prognostic factors for patients with ESCC and it is conducive to the early prediction of the prognosis of ESCC patients. Positive adjuvant therapy should be performed on patients with estimated shorter survival to improve their survival rate.
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