乙酰辅酶A羧化酶2基因高甲基化与肝细胞癌临床病理因素和生存期的关系  

Relationship between hypermethylation of ACACB gene and clinicopathological factors and survival of hepatocellular carcinoma

作　　者：董杰 杨松 杨浩 陈翔[2] 张万里[2] Dong Jie;Yang Song;Yang Hao;Chen Xiang;Zhang Wanli(Department of General Surgery,Honghu City People’s Hospital,Honghu 433200,China;Department of Digestive Oncology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]湖北省洪湖市人民医院普外科,433200 [2]华中科技大学同济医学院附属协和医院消化肿瘤外科,武汉430022

出　　处：《中华普通外科学文献（电子版）》2023年第6期433-437,共5页Chinese Archives of General Surgery(Electronic Edition)

摘　　要：目的检测肝细胞癌中乙酰辅酶A羧化酶2(ACACB)基因甲基化状态,并探讨其临床价值。方法选择90例肝细胞癌患者(HCC组)和45例肝脏良性疾病患者(对照组)为研究对象。分别将寡核苷酸(MON、UMON和CON)转染至Huh7细胞。采用甲基特异性PCR检测HCC组、对照组患者细胞ACACB基因甲基化状态;比较不同临床病理因素中ACACB基因甲基化频率的差异;CCK-8检测MON组、UMON组和CON组细胞增殖活性,Transwell检测三组Huh7细胞迁移侵袭数。结果HCC组肝细胞癌患者肿瘤组织ACACB基因甲基化频率显著高于癌旁组织和对照组(71.1%vs 6.7%和4.4%,P<0.05)。HepG2和Hep3B细胞中ACACB基因为甲基化状态,在Huh7细胞中为未甲基化状态。HCC组中低分化、有淋巴结转移、肿瘤最大径≥10 cm、肿瘤数目≥2个和Ⅲ期的ACACB基因甲基化频率显著高于中-高分化、无淋巴结转移、肿瘤最大径<10 cm、肿瘤数目1个和Ⅰ+Ⅱ期患者(均P<0.05)。ACACB基因甲基化患者中位生存期显著短于未甲基化患者[(34.7±5.2)个月vs(38.1±5.7)个月,P<0.05]。MON寡核苷酸可诱导Huh7细胞ACACB基因甲基化,MON组Huh7细胞d3、d5、d7吸光值和细胞迁移侵袭数均显著高于UMON组和CON组(均P<0.05)。结论肝细胞癌中ACACB基因处于高甲基化状态,与肿瘤分化程度、淋巴结转移、肿瘤最大径、肿瘤数目、TNM分期和生存期有关,可为肝细胞癌患者病情和预后评估提供基因水平的证据。Objective To detect the methylation status of acetyl-CoA carboxylaseβ(ACACB)gene in hepatocellular carcinoma and explore its clinical value.Methods 90 patients with hepatocellular carcinoma(HCC group)and 45 patients with benign liver diseases(control group)were selected as the research objects.Oligonucleotides(MON,UMON,and CON)were transfected into Huh7 cells,respectively.Methyl-specific PCR was used to detect the methylation of ACACB gene.The differences of ACACB gene’s methylation rate under different clinicopathological factors were studied and compared.CCK-8 was used to detect the cell proliferation in MON group,UMON group and CON group;cell migration and invasion numbers in the three groups were detected with Transwell.Results The methylation rate of ACACB gene in tumor tissue of HCC group was significantly higher than that of paracancerous tissue and control group(71.1%vs 6.7% and 4.4%,respectively,P<0.05).ACACB gene was methylated in HepG2 and Hep3B cells.Patients with poor differentiation,lymph node metastasis,maximum tumor diameter≥10 cm,the number of tumors≥2,and stage had significantly higher ACACB gene methylation rates than patients with moderately well-differentiated patients,no lymph node metastasis,maximum tumor diameter<10 cm,one tumor and stageⅠ+Ⅱ(all P<0.05).The median survival time of patients with ACACB gene methylation was significantly shorter than that of ACACB gene unmethylation patients[(34.7±5.2)months vs(38.1±5.7)months,P<0.05].MON oligonucleotides could induce ACACB gene methylation in Huh7 cells,the absorbance value on d3,d5,d7 cell and migration and invasion number of Huh7 cells in MON group were significantly higher than those in UMON group and CON group(all P<0.05).Conclusions The ACACB gene in hepatocellular carcinoma is in a hypermethylated state,which is related to the degree of tumor differentiation,lymph node metastasis,maximum tumor diameter,tumor number,TNM stage and survival time,providing evidences at the gene level for the assessment of the condition and pro

关 键 词：肝细胞癌 ACACB 甲基化 临床病理因素 生存期 

分 类 号：R73[医药卫生—肿瘤]