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中国癌症防治杂志

中国癌症防治杂志 ›› 2012, Vol. 4 ›› Issue (2): 110-114.doi: 10.3969/j.issn.1674-5671.2012.02.04

• 肝癌专栏 • 上一篇    下一篇

 广西乙肝病毒/黄曲霉毒素B1双暴露人肝细胞癌中PTEN mRNA表达及突变的初步研究

  

  1. 广西医科大学附属肿瘤医院肝胆外科；广西医科大学研究生学院；广西医科大学第一附属 医院肝胆血管外科
  • 出版日期:2012-06-25 发布日期:2012-07-03
  • 通讯作者: 游雪梅 E-mail:you_xuemei@163.com

PTEN genetic mutations and mRNA expression in cases of human hepatocellular carcino-ma exposed to hepatatitis B virus and aflatoxin B1 in Guangxi

  • Online:2012-06-25 Published:2012-07-03

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摘要： 目的 探讨乙肝病毒/黄曲霉毒素B1双暴露相关肝细胞性肝癌（HCC）中PTEN基因的突变特点及其mRNA的表达水平。方法 108例HCC来自广西不同地区样本，按照乙肝病毒与黄曲霉毒素的暴露情况，分为4个亚组：A组:HBV（+）/AFB1-DNA （+），共48例；B组：HBV（+）/AFB1-DNA （-），共27例；C组: HBV（-）/AFB1-DNA （+），共 19例；D组：HBV（-）/AFB1-DNA （-），共14例。采用PCR联合基因直接测序法，检测108例肝癌组织中PTEN基因第4、5、8外显子的突变情况。同时采用RT-PCR法检测其基因mRNA的表达状况。结果 ①PTEN基因第4、5、8外显子测序结果未发现发生在外显子上的突变。但在第4外显子与第4内含子交界处有61例发生大片段的缺失，缺失率为56.4%。②PTEN缺失率在A、B、C、D组中分别为60.4%、62.9%、47.3%和46.6%，其差异在4个亚组间均无统计学意义（P ＞0.05）。③PTEN mRNA在4个亚组中的表达半定量灰度值分别为：A组: 0.54±0.13；B组:0.59±0.16；C组:0.97±0.16；D组: 0.92±0.13。其中，A、B组分别与C、D组相比，其差异均具有统计学意义（PAC=0.002，PAD=0.032，PBC=0.000， PBD=0.011）。结论 在广西乙型肝炎病毒/黄曲霉毒素B1的双暴露肝细胞癌中，PTEN mRNA的表达下调是一个常见的分子生物学事件，PTEN mRNA表达下调可能主要与HBV感染有关。AFB1对PTEN mRNA的表达下调可能有协同作用。

关键词: 肝肿瘤, 乙肝病毒, 黄曲霉毒素B1, PTEN

Abstract: Objective To explore gene mutations and mRNA expression of PTEN in cases of hepatocellular carcinoma （HCC） exvposed to both hepatitis B virus and aflatoxin B1 （HBV/AFB1）. Methods A total of 108 cases of HCC from different districts of Guangxi were divided into 4 groups according to their exposure to HBV and AFB1：group A，HBV（+）/AFB1-DNA（+），48 cases；group B，HBV （+）/AFB1-DNA（-），27 cases；group C，HBV（-）/AFB1-DNA（+），19 cases；and group D，HBV（-）/AFB1-DNA（-），14 cases.PTEN mutations in exons 4，5，and 8 were detected by PCR and direct sequencing，and mRNA expression was analyzed by RT-PCR. Results PTEN mutations in exons 4，5，or 8 were not found in any of the cases. However，a large deletion at the junction of exon 4 and intron 4 was found in 61 cases，corresponding to a deletion rate of 56.4%.The rate of PTEN deletion was 60.4% in group A, 62.9% in group B，47.3% in group C and 46.6% in group D.The deletion rate was not statistically significant among the four sub-groups.Semi-quantitative gray values of the PTEN mRNA expression assay were as follows： group A，0.54 ± 0.13；group B，0.59± 0.16；group C，0.97 ± 0.16；group D，0.92 ± 0.13. The pair of groups A/B and the pair C/D differed significantly from each another in PTEN mRNA expression（PAC=0.002，PAD=0.032，PBC=0.000，PBD=0.011）. Conclusions Down-regulation of PTEN mRNA expression is a frequent molecular event in HCC involving double exposure to HBV/AFB1 in Guangxi，and it may be related to HBV infection.AFB1 and HBV may act synergistically to down-regulate PTEN mRNA levels.

Key words: Liver neoplasms, Hepatitis B virus, Aflatoxin B1, PTEN