Association between A-kinase anchor proteins 12 methylation and recurrence of hepatocellular carcinoma
10.3760/cma.j.issn.0253-9624.2017.09.014
- VernacularTitle: A激酶锚定蛋白12基因甲基化与原发性肝癌复发的关系研究
- Author:
Zhaojun LIU
1
;
Wei LIU
;
Chenghua CUI
;
Liankun GU
;
Baocai XING
;
Dajun DENG
Author Information
1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
- Publication Type:Journal Article
- Keywords:
Liver neoplasms;
DNA methylation;
Recurrence;
AKAP12
- From:
Chinese Journal of Preventive Medicine
2017;51(9):848-852
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the association between the AKAP12 promoter methylation and recurrence of hepatocellular carcinoma.
Methods:A total of 142 primary liver cancer patients underwent surgery in department of Hepatobiliary surgery in Peking University Cancer Hospital from 2003 to 2009 were selected as subjects in the survey; with the inclusion criteria as hepatocellular carcinoma, no cancer cells were observed in the surgical margin(SM) samples. All patients had neither lymph nor distant metastasis at the time of surgery, and receiving complete follow-up data for at least 3 years. By the end of May 2014, a total of 75 patients had relapsed of whom 71 died and there were no lost. All samples were acquired from the frozen surgical tissues. Genomic DNA was extracted using phenol/chloroform method and performed bisulfite modification following with polymerase chain reaction (PCR). AKAP12 methylation in hepatoma and the corresponding SM samples from 142 patients was determined by denature high-performance liquid chromatography (DHPLC) and bisulfite clone sequencing. Kaplan-Meier and Cox proportion hazard regression model were used to identify the factors related to the survival time.
Results:In 142 cases, 125 patients (88.0%) were male and 17 (12.0%) cases were female. The median age was 52.5 years, ranging from 34 years to 76 years. AKAP12 methylation-positive rate was significantly higher in hepatomas than SMs (54.9% vs. 10.2%, P<0.001). Patients with AKAP12 methylation-positive had less risk of the recurrence (HR=0.62, 95%CI: 0.39-0.99); with tumor diameter more than 5 cm (HR=1.53, 95%CI: 1.00-2.50),portal vein invasion(HR=4.53, 95% CI:2.69-7.64) increased the recurrence risk. Moreover, portal vein invasion had a higher risk of death (HR=2.98, 95% CI: 1.73-4.98).
Conclusion:There was significant association between AKAP12 DNA methylation and low risk of recurrence and long progression-free survival of hepatocellular carcinoma patients.
