The significance of aberrant CHFR methylation for clinical response to microtubule inhibitors in gastric cancer
The significance of aberrant CHFR methylation for clinical response to microtubule inhibitors in gastric cancer
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DOI：
10.1007/s00535-005-1732-7
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发表时间：
2006-02-01
影响因子：
6.3
通讯作者：
Miyazaki, K
中科院分区：
文献类型：
--
作者：
Koga, Y;Kitajima, Y;Miyazaki, K
背景我们研究了CHFR（checkpoint with FHA and RING finger）基因甲基化与胃癌对微管抑制剂（MI）反应的相关性。方法.我们检查了9种胃癌细胞系和46份来自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）确定启动子甲基化。通过定量逆转录-PCR估计CHFR mRNA表达。通过标准MTT法测定MI诱导的生长抑制。结果在9个胃癌细胞系中，有3个细胞系的CHFR表达被异常启动子甲基化所沉默。CHFR mRNA表达水平与MI处理的IC 50密切相关（R = 0.889，P = 0.005）。在46例胃癌患者中，24例（52%）出现CHFR异常甲基化。其中12例患者因肿瘤晚期或术后复发而接受MI治疗。CHFR甲基化患者对MI治疗的应答率为29%，而无甲基化患者为20%。然而，7例甲基化CHFR肿瘤患者中有6例（86%）表现出一定程度的消退或无进展，而5例非甲基化CHFR肿瘤患者中有4例（80%）表现出进行性恶化。结论.这些观察结果表明，CHFR甲基化可能是一种临床上有用的方法来预测胃癌对MI治疗的反应性。
Background. We studied the correlations between CHFR (checkpoint with FHA and RING finger) gene methylation and responses to microtubule inhibitors (MI) in gastric cancer. Methods. 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. Results. 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 IC50 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. Conclusions. These observations indicated that CHFR methylation may be a clinically useful approach to predict the responsiveness of gastric cancers to treatment with MI.