Zhang Yaojun, Huang Junting, Chen Jinbin, Yang Keli, Chen Jiancong, Xu Li, Zhou Zhongguo, Chen Minshan
Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
Cancer Manag Res. 2018 Mar 27;10:599-611. doi: 10.2147/CMAR.S160047. eCollection 2018.
Although hepatitis B virus (HBV) is still one of the most common etiological factors for hepatocellular carcinoma (HCC), the association between the HBV mutations and the clinical characteristics and prognosis of HBV-related HCC patients (HBV-HCC) after surgical resection remains largely unknown.
A cohort of 131 consecutive patients who received hepatectomy for HBV-HCC were retrospectively enrolled. The HBV genotype and 14 genomic mutations, which have been reported to relate to HCC in liver samples, were sequenced. The associations between the genomic mutations and clinical characteristics and outcomes were analyzed.
Both A1762T/G1764A mutation and Pre S deletion related to worse overall survival (OS, =0.040 and <0.001, respectively) and disease-free survival (DFS, =0.040 and <0.001, respectively), G1899A mutation related to worse OS (=0.030), A1762T/G1764A mutation correlated with tumor size (=0.204, =0.019), G1899A mutation correlated with vascular invasion (=0.332, <0.001), and Pre S deletion correlated with alpha-fetoprotein (AFP; =0.254, =0.003) positively. Multivariate analysis with Cox proportional hazards model revealed that both A1762T/G1764A mutation and Pre S deletion were independent prognostic factors for OS (hazard ratio [HR]=3.701, 95% CI=1.390-9.855, =0.009, and HR=4.816, 95% CI=2.311-10.032, <0.001, respectively) and DFS (HR=3.245, 95% CI=1.400-7.521, =0.006, and HR=2.437, 95% CI=1.311-4.530, <0.001, respectively), and patients with dual mutations were found to have the worst OS and DFS (<0.001 and <0.001, respectively). Patients with A1762T/G1764A mutation or Pre S deletion were more likely to have early recurrence (=0.042 and =0.019, respectively).
HBV DNA genomic mutations in A1762T/G1764A and Pre S deletion were associated with worse prognoses and early recurrence for HBV-HCC patients after surgery.
尽管乙型肝炎病毒(HBV)仍是肝细胞癌(HCC)最常见的病因之一,但手术切除后HBV突变与HBV相关HCC患者(HBV-HCC)的临床特征及预后之间的关联仍不清楚。
回顾性纳入131例连续接受肝切除术治疗HBV-HCC的患者。对肝组织样本中已报道的与HCC相关的HBV基因型及14个基因组突变进行测序。分析基因组突变与临床特征及预后的相关性。
A1762T/G1764A突变和前S区缺失均与较差的总生存期(OS,分别为P=0.040和P<0.001)及无病生存期(DFS,分别为P=0.040和P<0.001)相关,G1899A突变与较差的OS相关(P=0.030),A1762T/G1764A突变与肿瘤大小相关(r=0.204,P=0.019),G1899A突变与血管侵犯相关(r=0.332,P<0.001),前S区缺失与甲胎蛋白(AFP;r=0.254,P=0.003)呈正相关。Cox比例风险模型多因素分析显示,A1762T/G1764A突变和前S区缺失均为OS(风险比[HR]=3.701,95%可信区间[CI]=1.390-9.855,P=0.009,以及HR=4.816,95%CI=2.311-10.032,P<0.001,分别)和DFS(HR=3.245,95%CI=1.400-7.521,P=0.006,以及HR=2.437,95%CI=1.311-4.530,P<0.001,分别)的独立预后因素,且双突变患者的OS和DFS最差(分别为P<0.001和P<0.001)。发生A1762T/G1764A突变或前S区缺失的患者更易出现早期复发(分别为P=0.042和P=0.019)。
A1762T/G1764A和前S区缺失的HBV DNA基因组突变与HBV-HCC患者术后较差的预后及早期复发相关。