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.


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).


CONCLUSIONS
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.
Yoshida
Kazuhiro
K
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Hamai
Yoichi
Y
Suzuki
Takahisa
T
Sanada
Yuichi
Y
Oue
Naohide
N
Yasui
Wataru
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D000077143:Docetaxel; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010094:Oxonic Acid / Q000008:administration & dosage; D017239:Paclitaxel / Q000627:therapeutic use*; D000075223:Poly-ADP-Ribose Binding Proteins; D011725:Pyridines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D044767:Ubiquitin-Protein Ligases
D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D004338:Drug Combinations; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011725:Pyridines; D012333:RNA, Messenger; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases; D017239:Paclitaxel