Estrogen receptor 1 gene as a tumor suppressor gene in hepatocellular carcinoma detected by triple-combination array analysis
Estrogen receptor 1 gene as a tumor suppressor gene in hepatocellular carcinoma detected by triple-combination array analysis
复制标题
DOI：
10.3892/ijo.2013.1951
复制
发表时间：
2013-07-01
影响因子：
5.2
通讯作者：
Kodera, Yasuhiro
中科院分区：
文献类型：
--
作者：
Hishida, Mitsuhiro;Nomoto, Shuji;Kodera, Yasuhiro
肝细胞癌是世界上与癌症相关的死亡的前五大原因之一。肝癌治疗的最新进展仍然不足以治愈不能切除的疾病或预防肝癌。因此，需要持续的努力来加深对该病发病机制的了解。全基因组的基因表达谱分析现在可以检测到被肝细胞癌修饰的各种候选基因。我们开发了一种识别肿瘤抑制基因的新技术，三组合阵列分析，它结合了基因表达谱、单核苷酸多态和甲基化阵列来识别表达改变的基因。利用肝细胞癌组织样本，进行三组合阵列分析以确定候选抑癌基因。随后，对48例肝细胞癌患者的样本进行了定量聚合酶链式反应和甲基化特异性聚合酶链式反应，以进一步阐明该基因的临床相关性。雌激素受体1(ESR1)是一种候选抑癌基因。在48例临床标本中，40例(83.3%)ESR1基因启动子甲基化。在24例(50%)肝细胞癌标本中，ESR1基因的表达水平下降了90%。低表达与肝损伤评分高、肝内门静脉受侵、肿瘤大小(直径3 cm)及乙肝病毒感染显著相关。本研究代表了另一个例子，即三重组合阵列是检测疾病中表达改变的基因的一种方便的技术。ESR1基因被确定为肝癌的候选抑癌基因，进一步验证是有必要的。
Hepatocellular carcinoma (HCC) is one of the top five causes of cancer-related deaths worldwide. Recent developments in the treatment of HCC remain insufficient to cure unresectable disease or to prevent HCC. Consistent efforts are, therefore, needed to deepen understanding of pathogenesis of the disease. Genome-wide gene expression profile analyses can now detect various candidate genes that are modified by HCC. We have developed a new technique to identify tumor suppressor genes, triple-combination array analysis, which combines gene expression profiles, single nucleotide polymorphism and methylation arrays to identify genes with altered expression. Using HCC tissue samples, triple-combination array analysis was performed to identify a candidate tumor suppressor gene. Subsequently, samples from 48 HCC patients were subjected to quantitative polymerase chain reaction (qPCR) and methylation-specific PCR to further elucidate clinical relevance of the gene. Estrogen receptor 1 (ESR1) was detected as a candidate tumor suppressor gene. Of the 48 clinical samples, 40 (83.3%) showed ESR1 promoter hypermethylation. In 24 (50%) HCC samples, the expression levels of the ESR1 gene was decreased by >90%. The decreased expression was significantly related to high liver damage score, pathological invasion of the intrahepatic portal vein, the size of tumor (>3 cm in diameter) and hepatitis B virus infection. The present study represents another example that triple-combination array is a convenient technique for detecting genes with altered expression in disease. The ESR1 gene was identified as a candidate tumor suppressor gene in HCC and further validation is warranted.