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J Gastroenterol. 2006 Feb;41(2):133-9.

The significance of aberrant CHFR methylation for clinical response to microtubule inhibitors in gastric cancer.

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1
Department of Surgery, Saga University Faculty of Medicine, Nabeshima 5-1-1, Saga 849-8501, Japan.

Abstract

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 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.

CONCLUSIONS:

These observations indicated that CHFR methylation may be a clinically useful approach to predict the responsiveness of gastric cancers to treatment with MI.

PMID:
16568372
DOI:
10.1007/s00535-005-1732-7
[Indexed for MEDLINE]
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