[Association between A-kinase anchor proteins 12 methylation and recurrence of hepatocellular carcinoma].

• DOI: 10.3760/cma.j.issn.0253-9624.2017.09.014
• Publication Date: 2017-09-06
• Authors: Z J Liu; W Liu; Chanjuan Cui; Liugen Gu; Bao-Cai Xing; Dajun Deng
• Keywords: Adult; Male; Carcinoma, Hepatocellular; Recurrence; Liver Neoplasms; A Kinase Anchor Proteins; Humans; Cell Cycle Proteins; Female; DNA Methylation; Middle Aged; Promoter Regions, Genetic; Aged

Objective: To study the association between AKAP12 promoter methylation and recurrence of hepatocellular carcinoma. Methods: A total 142 primary liver cancer patients underwent surgery in department Hepatobiliary Peking University Cancer Hospital from 2003 to 2009 were selected as subjects survey; with inclusion criteria carcinoma, no cells observed surgical margin(SM) samples. All had neither lymph nor distant metastasis at time surgery, receiving complete follow-up data for least 3 years. By end May 2014, a 75 relapsed whom 71 died there lost. samples acquired frozen tissues. Genomic DNA was extracted using phenol/chloroform method performed bisulfite modification following polymerase chain reaction (PCR). hepatoma corresponding SM determined by denature high-performance liquid chromatography (DHPLC) clone sequencing. Kaplan-Meier Cox proportion hazard regression model used identify factors related survival time. Results: In cases, 125 (88.0%) male 17 (12.0%) cases female. The median age 52.5 years, ranging 34 years 76 methylation-positive rate significantly higher hepatomas than SMs (54.9% vs. 10.2%, P<0.001). Patients less risk (HR=0.62, 95%CI: 0.39-0.99); tumor diameter more 5 cm (HR=1.53, 1.00-2.50),portal vein invasion(HR=4.53, 95% CI:2.69-7.64) increased risk. Moreover, portal invasion death (HR=2.98, CI: 1.73-4.98). Conclusion: There significant low long progression-free carcinoma patients.目的： 探讨A激酶锚定蛋白12(AKAP12)甲基化与原发性肝癌复发的关系。 方法： 于2003—2009年，以在北京大学肿瘤医院肝胆外科接受手术治疗的原发性肝癌患者作为研究对象，对其进行≥3年的随访。纳入标准：肝细胞癌患者，经鉴定切缘组织无肿瘤细胞存在；手术时无淋巴结转移及远处转移；有完整的临床资料，共142例。截至2014年5月随访结束，共有75例研究对象复发，其中71例死亡，无失访。从冰冻手术标本中获取研究对象的肿瘤组织及切缘组织，采用酚-氯仿法提取DNA并修饰后进行PCR扩增，对PCR产物进行克隆并测序分析，应用变性高效液相色谱检测研究对象肿瘤组织和肿瘤旁切缘正常组织AKAP12基因的甲基化状态。采用Log-rank检验对研究对象生存时间进行单因素分析；采用多因素Cox比例风险模型分析研究对象生存时间差异的影响因素。 结果： 142例研究对象中，男性125例（88.0%），年龄为34~76岁，中位年龄是52.5岁。肿瘤组织中AKAP12甲基化阳性率（54.9%，78/142）高于切缘组织中AKAP12甲基化阳性率（10.2%，6/59）。与AKAP12甲基化阴性者相比，AKAP12甲基化阳性者原发性肝癌复发风险较低HR=0.62，95%CI：0.39~0.99；与肿瘤直径≤5 cm者相比，肿瘤直径>5 cm者原发性肝癌复发风险较高HR=1.53，95%CI：1.00~2.50；与无门脉侵犯者相比，有门脉侵犯者原发性肝癌复发风险较高HR=4.53，95%CI：2.69~7.64。与无门脉侵犯者相比，有门脉侵犯者死亡风险较高HR=2.98，95%CI：1.73~4.98。 结论： AKAP12甲基化与原发性肝癌的复发及无疾病生存时间相关。.