Sakai Mitsuru, Hibi Kenji, Kanazumi Naohito, Nomoto Shuji, Inoue Soichiro, Takeda Shin, Nakao Akimasa
Department of Surgery II, Graduate School of Medicine, Nagoya University, Japan.
Hepatogastroenterology. 2005 Nov-Dec;52(66):1854-7.
BACKGROUND/AIMS: Recently, aberrant methylation of the CHFR gene associated with gene silencing has been reported in several cancers. We examined the methylation status of the CHFR gene in primary hepatocellular carcinomas (HCCs) and evaluated the correlation between the methylation status and the malignancy of HCC.
We first examined the methylation status of the CHFR promoter region and mRNA expression in cancer cell lines. Next, we examined the methylation status of the CHFR gene in 62 primary HCCs and then investigated the correlation between CHFR methylation and the clinicopathological findings.
The cell line with CHFR promoter methylation showed a loss of CHFR expression that was restored after 5-aza-2'-deoxycytidine (5-aza-dC) treatment, suggesting that aberrant methylation of the CHFR gene was associated with gene silencing. CHFR methylation was detected in 22 of 62 (35%) primary HCCs, whereas no methylation was detected in noncancerous liver tissues. Furthermore, CHFR methylation was significantly associated with an infiltrative growth pattern (p=0.047) and an advanced stage (p=0.037).
Aberrant methylation of the CHFR gene is significantly correlated with the progression of HCC, suggesting that CHFR methylation might be a novel molecular marker to estimate the malignancy of this disease.
背景/目的：最近，有报道称在几种癌症中存在与基因沉默相关的CHFR基因异常甲基化。我们检测了原发性肝细胞癌（HCC）中CHFR基因的甲基化状态，并评估了甲基化状态与HCC恶性程度之间的相关性。
我们首先检测了癌细胞系中CHFR启动子区域的甲基化状态和mRNA表达。接下来，我们检测了62例原发性HCC中CHFR基因的甲基化状态，然后研究了CHFR甲基化与临床病理结果之间的相关性。
CHFR启动子甲基化的细胞系显示CHFR表达缺失，经5-氮杂-2'-脱氧胞苷（5-aza-dC）处理后恢复，表明CHFR基因的异常甲基化与基因沉默有关。62例原发性HCC中有22例（35%）检测到CHFR甲基化，而在非癌肝组织中未检测到甲基化。此外，CHFR甲基化与浸润性生长模式（p=0.047）和晚期（p=0.037）显著相关。
CHFR基因的异常甲基化与HCC的进展显著相关，提示CHFR甲基化可能是评估该疾病恶性程度的一种新的分子标志物。
