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中国汉族人群线粒体DNA含量、G10398A多态性、HPV感染与宫颈癌预后的关联分析

An association analysis between mitochondrial DNA content, G10398A polymorphism, HPV infection, and the prognosis of cervical cancer in the Chinese Han population.

作者信息

Feng Dali, Xu Hui, Li Xin, Wei Yuehua, Jiang Huangang, Xu Hong, Luo Aihua, Zhou Fuxiang

机构信息

Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.

Department of Radiation and Medical Oncology, The Second Hospital of Yichang, Yichang, China.

出版信息

Tumour Biol. 2016 Apr;37(4):5599-607. doi: 10.1007/s13277-015-4429-4. Epub 2015 Nov 14.

Abstract

The aim was to analyze quantitative (mitochondrial DNA (mtDNA) content) and qualitative (G10398A polymorphism) mtDNA alterations as well as human papillomavirus (HPV) infection in cervical cancer prognosis. One hundred and twenty-two cases of formalin-fixed paraffin-embedded cervical carcinoma specimens were collected from the Yichang Tumor Hospital and Zhongnan Hospital of Wuhan University in the recent 10 years together with medical records. A quantitative real-time PCR (RT-PCR) was used to determine the copy number of the mitochondrial DNA and HPV expression levels. G10398A polymorphism was determined by PCR-RFLP assay. The overall survival of patients with higher mtDNA content was significantly reduced compared with lower mtDNA content patients (P = 0.029). But there was no difference of prognosis between the mtDNA 10398 A allele and G allele. However, the Kaplan-Meier survival curve illustrated a significantly reduced overall survival in the patients with 10398A plus high mtDNA copy number compared with the other groups (P < 0.05). Although no association between HPV expression level and cervical cancer prognosis was observed, 10398A got increased mtDNA content compared with 10398G (P < 0.05) and 10398G displayed an increased HPV-positive rate compared with 10398A. Furthermore, HPV-18 and mtDNA content were positively related in the younger subgroup (≤45 years) (correlation coefficient = 0.456, P = 0.022). This study indicated that mtDNA content and HPV infection status are associated with cervical cancer prognosis. High mitochondrial DNA content plus 10398 A may be a marker of poor prognosis in cervical cancer. And mtDNA variation may potentially influence the predisposition to HPV infection and cervical carcinogenesis.

摘要

目的是分析定量(线粒体DNA(mtDNA)含量)和定性(G10398A多态性)mtDNA改变以及人乳头瘤病毒(HPV)感染与宫颈癌预后的关系。在最近10年里,从宜昌肿瘤医院和武汉大学中南医院收集了122例福尔马林固定石蜡包埋的宫颈癌标本,并收集了病历。采用定量实时聚合酶链反应(RT-PCR)测定线粒体DNA的拷贝数和HPV表达水平。通过PCR-RFLP分析确定G10398A多态性。与mtDNA含量较低的患者相比,mtDNA含量较高的患者总生存期显著缩短(P = 0.029)。但mtDNA 10398 A等位基因和G等位基因之间的预后无差异。然而,Kaplan-Meier生存曲线显示,与其他组相比,10398A加mtDNA高拷贝数患者的总生存期显著缩短(P < 0.05)。虽然未观察到HPV表达水平与宫颈癌预后之间的关联,但与10398G相比,10398A的mtDNA含量增加(P < 0.05),与10398A相比,10398G的HPV阳性率增加。此外,在较年轻亚组(≤45岁)中,HPV-18与mtDNA含量呈正相关(相关系数 = 0.456,P = 0.022)。本研究表明,mtDNA含量和HPV感染状态与宫颈癌预后相关。高线粒体DNA含量加10398 A可能是宫颈癌预后不良的一个标志物。并且mtDNA变异可能潜在影响HPV感染易感性和宫颈癌发生。

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