Underexpression of mRNA in human hepatocellular carcinoma focusing on eight loci
Underexpression of mRNA in human hepatocellular carcinoma focusing on eight loci
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DOI：
10.1053/jhep.2002.34851
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发表时间：
2002-08-01
期刊：
影响因子：
13.5
通讯作者：
Miyata, M
中科院分区：
文献类型：
--
作者：
Kinoshita, M;Miyata, M
与人肝细胞癌（HCC）相关的遗传改变先前已有报道，但不足以说明HCC与肝癌前疾病（如肝炎、肝纤维化和肝硬化）的差异。在本研究中，我们进行了差异基因显示分析（DGDA），以澄清与慢性病毒性肝炎肝细胞癌的发展过程中的基因表达变化相关的特定遗传变异。研究了四对手术切除的HCC和肝炎组织。我们发现，与同一患者的肝炎组织相比，肝癌组织中有1，028个表达序列标签（EST）减少或增加。核苷酸测序结果显示，它们包括GenBank数据库中的55个EST克隆，这些克隆被认为是HCC中特异性信使RNA（mRNA）表达改变的候选者。在排除9个编码线粒体DNA的EST后，我们对剩下的46个EST克隆进行了实时定量逆转录聚合酶链反应（RT-PCR）。我们发现20例原发性HCC组织中8种mRNA表达不足，其百分比高于先前研究中的发现，包括18例（90%）醛缩酶B（ALDO B），15例（75%）氨甲酰磷酸合成酶1（CPS 1），白蛋白（AL B），纤溶酶原（PLG）和EST 51549，细胞色素P450亚家族2 E1（CYP 2 E1）基因型13例（65%），人视黄醇结合蛋白4（RBP 4）基因型12例（60%），人有机阴离子转运蛋白C（OATP-C）基因型11例（55%）。总之，关键基因产物的低表达可能在HCC的发生和/或进展中是重要的。
Genetic alterations associated with human hepatocellular carcinoma (HCC) have been reported previously, but are not sufficient to specify differences of HCCs from precancerous diseases of the liver, such as hepatitis, hepatic fibrosis, and cirrhosis. In the present study, we performed differential gene display analysis (DGDA) to clarify the specific genetic alterations associated with gene expression changes in the course of development of HCC from chronic viral hepatitis. Four pairs of surgically resected HCCs and hepatitis tissues were investigated. We found 1,028 expression sequence tags (ESTs) that were decreased or increased in HCC tissues compared with hepatitis tissues in the same patient. Nucleotide sequencing showed that they included 55 EST clones in the GenBank database, which were considered candidates for specific messenger RNA (mRNA) expression alterations in HCCs. After excluding 9 ESTs that code mitochondrial DNA, we performed quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) for the 46 remaining EST clones. We found 8 mRNAs underexpressed in primary HCC tissues in 20 patients in higher percentages than found in previous studies, including 18 cases (90%) for aldolase B (ALDOB), 15 cases (75%) for carbamyl phosphate synthetase 1 (CPS1), albumin (ALB), plasminogen (PLG), and EST 51549,13 cases (65%) for cytochrome P450 subfamily 2E1 (CYP2E1),12 cases (60%) for human retinol-binding protein 4 (RBP4), and 11 cases (55%) for human organic anion transporter C (OATP-C) gene. In conclusion, underexpression of key gene products may be important in the development and/or progression of HCC.