DNA methylation of CHFR is not a predictor of the response to docetaxel and paclitaxel in advanced and recurrent gastric cancer.

BACKGROUND: Cell cycle checkpoint dysfunction is often associated with sensitivity to chemotherapeutic agents. In this study, the question of whether DNA methylation of CHFR, a mitotic checkpoint gene, can predict the response of advanced and recurrent gastric cancers (GCs) to docetaxel or paclitaxel was examined.
MATERIALS AND METHODS: In a retrospective study, 41 patients with GC treated with paclitaxel alone (n=12) or a combination of docetaxel and S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine, potassium oxonate) (n=29) were studied. The DNA methylation status of the CHFR gene was examined by combined bisulfite restriction analysis of DNAs from 41 GC tissues and the methylation status was compared to their sensitivity to chemotherapy. The levels of CHFR mRNA were measured by quantitative reverse transcription-PCR.
RESULTS: DNA methylation of CHFR was found in 15 (36.6%) out of the 41 GC samples and the levels of CHFR mRNA were associated with the methylation status of CHFR (p = 0.034). In 41 samples of corresponding non-neoplastic mucosae, no DNA methylation of CHFR was detected. Among 12 patients treated with paclitaxel alone, only 1 (20.0%) of the 5 patients with CHFR methylation had a partial response (PR) to paclitaxel, whereas 3 (42.9%) of the 7 patients without CHFR methylation had a PR to paclitaxel (p = 0.836). In 29 patients treated with a combination of S-1 and docetaxel, there was no clear association between the CHFR methylation status and response to chemotherapy (p = 0.092).
CONCLUSION: We conclude that the DNA methylation of CHFR alone cannot predict the response of advanced and recurrent GC to docetaxel or paclitaxel. Both paclitaxel and docetaxel may be effective for treatment of GC even if CHFR is expressed.