Koga Yasuo, Kitajima Yoshihiko, Miyoshi Atsushi, Sato Ken, Sato Seiji, Miyazaki Kohji
Department of Surgery, Saga University Faculty of Medicine, Nabeshima 5-1-1, Saga 849-8501, Japan.
J Gastroenterol. 2006 Feb;41(2):133-9. doi: 10.1007/s00535-005-1732-7.
We studied the correlations between CHFR (checkpoint with FHA and RING finger) gene methylation and responses to microtubule inhibitors (MI) in gastric cancer.
We examined 9 gastric cancer cell lines and 46 gastric cancer specimens from patients who underwent surgical resection. Promoter methylation was determined by methylation-specific polymerase chain reaction (MSP). CHFR mRNA expression was estimated by quantitative reverse transcription-PCR. The MI-induced growth inhibition was assayed by a standard MTT method.
CHFR expression was silenced by aberrant promoter methylation in 3 of 9 gastric cancer cell lines. The level of CHFR mRNA expression was closely correlated with IC(50) in the MI-treated cells (R=0.889, P=0.005). In 46 patients with gastric cancers, 24 (52%) presented aberrant CHFR methylation. Among them, 12 patients had received treatment with MI because of advanced-stage tumor or tumor recurrence after surgery. The responders to the MI treatment were 29% in patients with CHFR methylation and 20% in those without the methylation. However, 6 (86%) of 7 patients with methylated CHFR tumor showed some regression or no progression, whereas 4 (80%) of 5 patients with unmethylated CHFR tumor manifested progressive deterioration.
These observations indicated that CHFR methylation may be a clinically useful approach to predict the responsiveness of gastric cancers to treatment with MI.
我们研究了胃癌中CHFR（含FHA和RING结构域的细胞周期检查点蛋白）基因甲基化与对微管抑制剂（MI）反应之间的相关性。
我们检测了9种胃癌细胞系以及46例接受手术切除患者的胃癌标本。通过甲基化特异性聚合酶链反应（MSP）测定启动子甲基化情况。通过定量逆转录PCR评估CHFR mRNA表达。采用标准MTT法检测MI诱导的生长抑制作用。
9种胃癌细胞系中有3种因启动子异常甲基化导致CHFR表达沉默。CHFR mRNA表达水平与MI处理细胞中的IC(50)密切相关（R = 0.889，P = 0.005）。在46例胃癌患者中，24例（52%）存在CHFR异常甲基化。其中，12例患者因晚期肿瘤或术后肿瘤复发接受了MI治疗。CHFR甲基化患者中MI治疗的反应率为29%，未甲基化患者为20%。然而，7例CHFR肿瘤甲基化患者中有6例（86%）出现一定程度的肿瘤退缩或无进展，而5例CHFR肿瘤未甲基化患者中有4例（80%）病情进展恶化。
这些观察结果表明，CHFR甲基化可能是预测胃癌对MI治疗反应性的一种临床有用方法。
