Expression and Hypomethylation of α‐Fetoprotein Gene in Unicentric and Multicentric Human Hepatocellular Carcinomas
Expression and Hypomethylation of α‐Fetoprotein Gene in Unicentric and Multicentric Human Hepatocellular Carcinomas
复制标题
甲胎蛋白基因在单中心和多中心人肝细胞癌中的表达和低甲基化
作者：
S. Peng;H. Hsu;P. Lai;Po‐Tah Tsung;J. Chu;Po;Ding‐Shinn Chen
在 101 个切除的原发性肝细胞癌中研究了甲胎蛋白基因的信使 RNA 和 DNA 甲基化，其中 93 个是单中心的，8 个是多中心的。 55 个直径为 5 厘米或以下（小），46 个直径超过 5 厘米（大）。在 48.5% 的病例中，我们在肝细胞癌中检测到了甲胎蛋白信使 RNA，在大肝细胞癌 (60.9%) 中比小肝细胞癌 (38.2%；p < 0.00001) 更常见，但在任何非肿瘤肝脏中均未检测到。血清甲胎蛋白水平为 320 ng/ml 或以上、100 至 319 ng/ml 和低于 100 ng/ml 的患者中，分别有 83%、70% 和 6.8% 的患者检测到甲胎蛋白信使 RNA。这一发现表明，肝细胞癌中甲胎蛋白基因表达有助于肝细胞癌患者血清甲胎蛋白升高。 α-胎蛋白信使RNA在肝细胞癌和胎儿肝脏中出现为2.4 kb的主要条带，以及约6.5和3.6 kb的两个次要种类。在表达甲胎蛋白信使 RNA 的肝细胞癌中，78.3% 检测到甲胎蛋白基因 5' 端的低甲基化，但在未检测到甲胎蛋白信使 RNA 的肝细胞癌中，很少 (16.7%) 检测到 (p < 0.0003)。这一发现表明该基因 5' 区域的低甲基化与肝细胞癌中甲胎蛋白基因的重新表达有关。甲胎蛋白基因表达有助于区分单中心性和多中心性肝细胞癌，并有助于识别其他隐藏的分泌甲胎蛋白的肝细胞癌。甲胎蛋白基因表达更常见于 30 岁以下患者（100% vs. 41.2%；p < 0.002）、HBsAg 血清阳性患者（53.2% vs. 33.3%；p < 0.03）和低分化肝细胞癌患者（56% vs. 23.1%；p < 0.003）。表达甲胎蛋白信使 RNA 或血清甲胎蛋白升高的单中心小肝细胞癌患者的 2 年生存率比既不表达甲胎蛋白信使 RNA 又不血清甲胎蛋白升高的患者差（70.6% vs. 94.7%；p < 0.02）。我们的结论是，肝细胞癌中甲胎蛋白基因的表达具有生物学意义。 （肝病学 1993；17：35–41。）
The messenger RNA and DNA methylation of the α‐fetoprotein gene were studied in 101 resected primary hepatocellular carcinomas, of which 93 were unicentric and 8 were multicentric. Fifty‐five were 5 cm or less in diameter (small) and 46 were more than 5 cm in diameter (large). In 48.5% of the cases, we detected α‐fetoprotein messenger RNA in hepatocellular carcinomas, more frequently in large (60.9%) than in small (38.2%; p < 0.00001) but not in any of the nontumorous livers. The α‐fetoprotein messenger RNA was detected in 83%, 70% and 6.8% of patients with serum α‐fetoprotein levels of 320 ng/ml or more, 100 to 319 ng/ml and less than 100 ng/ml, respectively. This finding suggests that α‐fetoprotein gene expression in hepatocellular carcinoma contributes to the serum α‐fetoprotein elevation in patients with hepatocellular carcinoma. α‐Fetoprotein messenger RNA appeared as a major band of 2.4 kb, with two minor species of about 6.5 and 3.6 kb in the hepatocellular carcinoma and the fetal liver. Hypomethylation of the 5′ end of the α‐fetoprotein gene was detected in 78.3% of hepatocellular carcinomas expressing α‐fetoprotein messenger RNA but infrequently (16.7%) in hepatocellular carcinomas with no detectable α‐fetoprotein messenger RNA (p < 0.0003). This finding suggests that hypomethylation at the 5′ region of the gene is associated with α‐fetoprotein gene reexpression in hepatocellular carcinoma. The α‐fetoprotein gene expression helped to differentiate unicentric from multicentric hepatocellular carcinomas and to identify other hidden α‐fetoprotein‐secreting hepatocellular carcinomas. The α‐fetoprotein gene expression occurred more often in patients younger than 30 yr old (100% vs. 41.2%; p < 0.002), in HBsAg‐seropositive patients (53.2% vs. 33.3%; p < 0.03) and in patients with poorly differentiated hepatocellular carcinoma (56% vs. 23.1%; p < 0.003). Patients with unicentric small hepatocellular carcinomas expressing α‐fetoprotein messenger RNA or serum α‐fetoprotein elevation had a worse 2‐yr survival rate than those with neither α‐fetoprotein messenger RNA expression nor serum α‐fetoprotein elevation (70.6% vs. 94.7%; p < 0.02). We conclude that the α‐fetoprotein gene expression in hepatocellular carcinoma possesses biological significance. (HEPATOLOGY 1993;17:35–41.)
同基因大鼠肝癌和肝细胞系中甲胎蛋白基因的甲基化。
DOI：
10.1016/0006-291x(87)91374-x
发表时间：
1987
影响因子：
3.1
作者：
Sakuma,K;Cook,JR;Smith,CL;Chiu,JF
通讯作者：
Chiu,JF