Open AccessMethylated BNIP3 gene in colorectal cancer prognosis
Author(s) -
Sayaka Shimizu,
Satoru Iida,
Megumi Ishiguro,
Hiroyuki Uetake,
Toshiaki Ishikawa,
Yoko Takagi,
Hirotoshi Kobayashi,
Tetsuro Higuchi,
Masayuki Enomoto,
Kaoru Mogushi,
Hiroshi Mizushima,
Hiroshi Tanaka,
Kenichi Sugihara
Publication year - 2010
Publication title -
oncology letters
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.766
H-Index - 54
eISSN - 1792-1082
pISSN - 1792-1074
DOI - 10.3892/ol_00000153
Subject(s) - methylation , irinotecan , dna methylation , colorectal cancer , cancer research , apoptosis , oncogene , biology , cancer , microarray analysis techniques , microarray , gene , oncology , cell cycle , medicine , gene expression , genetics
The DNA methylation of apoptosis-related genes in various cancers contributes to the disruption of the apoptotic pathway and results in resistance to chemotherapeutic agents. Irinotecan (CPT-11) is one of the key chemotherapy drugs used to treat metastatic colorectal cancer (CRC). However, a number of metastatic CRC patients do not benefit from this drug. Thus, the identification of molecular genetic parameters associated with the response to CPT-11 is of interest. To identify apoptosis-related genes that may contribute to CPT-11 resistance, microarray analysis was conducted using colon cancer cells in which 5-aza-2'deoxycytidine (DAC) enhanced sensitivity to CPT-11. Microarray analysis identified 10 apoptosis-related genes that were up-regulated following treatment with DAC. Among the genes, Bcl-2/adenovirus E1B 19 kDa protein interacting protein 3 (BNIP3), a Bcl-2 family pro-apoptotic protein, was identified as being involved in CPT-11 resistance following methylation of its promoter. An analysis of 112 primary CRC cases revealed that approximately 58% of cases showed BNIP3 methylation, and that patients with methylation exhibited a poorer outcome compared to those without methylation. In addition, in 30 patients who received first-line CPT-11 chemotherapy, patients with methylation exhibited resistance to chemotherapy compared to patients with no methylation. The results suggest that methylation of BNIP3 is a predictive factor in the prognosis and response to CPT-11 treatment in CRC patients.