中国癌症防治杂志Issue(3)：201-209,210,10.DOI:10.3969/j.issn.1674-5671.2013.03.04
广西地区乙肝病毒/黄曲霉毒素B1双暴露相关性肝细胞性肝癌微阵列比较基因组学的研究
Array-based comparative genomic hybridization analysis of patients with hepatocellular carcinoma related to hepatitis B virus and aflatoxin B1 exposure in Guangxi,China
摘要
Abstract
Objective To investigate genetic changes in individuals that may influence development of hepatocellular carcinoma (HCC)associated with hepatitis B virus (HBV)and exposure to aflatoxin B1 (AFB1). Method Patients with HCC were divided into four groups based on HBV infection and AFB1 exposure status:HBV(+)/AFB1(+),n=10;HBV(+)/AFB1(-),n=10;HBV(-)/AFB1(+), n=6;HBV(-)/AFB1(-),n=6.Array-based comparative genomic hybridization(Array CGH)was carried out on tumor tissue to identify genome-wide genetic changes. Result Among all 32 tissue samples,573 CNAs were identified,comprising 184 gains and 389 losses. Frequent gains were observed in the following regions:1q,4p,5p,6p,7p,8q,10p,17q,20p,20q and X.Frequent losses were observed in the following regions:1p,2q,4q,8p,9p,10q,11q,13q,14q,16p,16q,17p,19p,19q,21q,22q and Y.A total of 25 RARs were de-tected:8 RAR gains were 1q21.1-q44,5p13.2-p15.3,6p12.1-p25.2,7q21.1-q35,8q11.2-q24.3,17q12-q25.2,18q12.3-q22.3 and X;17 RARs losses were 1p31.1-p36.2,2q23.2-q37.2,4q12-q35.2,6q14.1-q26,8p12-p23.2,9p21.1-p24.2,10q21.3-q26.2,13q12.1-q21.1, 14q21.3-q32.2,16p12.1-p13.2,16q12.1-q24.1,17p12-p13.3,19p13.1-p13.3,19q13.2-q13.4,21q21.3-q22.2,22q11.2-q13.2 and Y.Loss of 8p12-p23.2 was associated with higher TNM tumor stage(TNM I-II:38.9% vs TNM Ⅲ:92.9%;P=0.038)and shorter tumor-free survival(P=0.045).Loss of 4q13.3-q35.2 and 13q12.1-q21.2 and gain of 7q11.2-q35 occurred at higher frequency among HBV(+)/AFB1(+)patients than among the other groups. Univariate analysis found tumor-free survival to be associated with tumor size,serum AFP,BCLC,TNM stage,invasion and metastasis,and loss of 8p12-p23.2(all P<0.05).Multivariate analysis revealed three of these fac-tors to be independently associated with tumor-free survival:serum AFP(≥400),TNM stage,and loss of 8p12-p23.2(all P≤0.045). Conclusion Several chromosomal alterations were identified in the genomes of individuals with HCC in Guangxi.Loss of 19p13.1-p13.3 may be a characteristic feature of the disease in this part of China. Loss of 8p12-p23.2 may occur later during HCC progression and is associated with shorter tumor-free survival. Loss of 4q12-q35.2 and 13q12.1-q21.1 and gain of 7q21.1-q35 may be associated with the synergistic hepatocarcinogenic effect of HBV infection combined with AFB1 exposure.关键词
肝肿瘤/乙肝病毒/黄曲霉毒素B1/染色体/Array CGHKey words
Liver neoplasms/Hepatitis B virus/Aflatoxin B1/Chromosome/Array CGH分类
医药卫生引用本文复制引用
齐鲁楠,陈圆圆,陈祖舜,白涛,朱海,彭涛,黎乐群..广西地区乙肝病毒/黄曲霉毒素B1双暴露相关性肝细胞性肝癌微阵列比较基因组学的研究[J].中国癌症防治杂志,2013,(3):201-209,210,10.基金项目
国家自然科学基金资助项目（30960021）；广西自然科学基金资助项目（桂科基0640101）；广西科学研究与技术开发计划项目 （）
