Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer

被引：24

作者：

Baba, H. ^{[1
]}

Watanabe, M. ^{[1
]}

Okabe, H. ^{[1
]}

Miyamoto, Y. ^{[1
]}

Sakamoto, Y. ^{[1
]}

Baba, Y. ^{[1
]}

Iwatsuki, M. ^{[1
]}

Chikamoto, A. ^{[1
]}

Beppu, T. ^{[1
]}

机构：

[1] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto 8608556, Japan

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 107卷 / 12期

关键词：

DPD; ERCC1; metastatic colorectal cancer; National Cancer Institute; oxaliplatin; STEM-CELLS; GENE-EXPRESSION; FLUOROURACIL FAILURE; RANDOMIZED-TRIAL; HETEROGENEITY; IRINOTECAN; MUTATIONS; MARKER; EGFR; KRAS;

D O I：

10.1038/bjc.2012.502

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: The updated randomised phase 2/3 FIRIS study demonstrated the noninferiority of IRIS (irinotecan and S-1) to FOLFIRI (irinotecan, folinic acid, and 5-FU) for metastatic colorectal cancer. Meanwhile, in the subset analysis including patients who previously have undergone oxaliplatin-containing chemotherapy, the IRIS group showed longer survival than the FOLFIRI group. However, the molecular mechanism underlying this result is still unknown. METHODS: The National Cancer Institute 60 (NCI60) cell line panel data were utilised to build the hypothesis. A total of 45 irinotecan-naive metastatic colorectal cancer patients who had undergone hepatic resection were included for the validation study. The mRNA expressions of excision repair cross-complementing group 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), and topoisomerase-1 (TOP1) were evaluated by quantitative RT-PCR. The expressions of ERCC1 and DPD were also evaluated by immunohistochemistry. RESULTS: Sensitivity to oxaliplatin in 60 cell lines was significantly correlated with that of 5-FU. Resistant cells to oxaliplatin showed significantly higher ERCC1 and DPD expression than sensitive cells. In validation study, ERCC1 and DPD but not TOP1 expressions in cancer cells were significantly higher in FOLFOX (oxaliplatin, folinic acid, and 5-FU)-treated patients (N = 24) than nontreated patients (N = 21). The ERCC1 and DPD protein expressions were also significantly higher in FOLFOX-treated patients. CONCLUSION: The ERCC1 and DPD expression levels at both mRNA and protein levels were significantly higher in patients with oxaliplatin as a first-line chemotherapy than those without oxaliplatin. The IRIS regimens with the DPD inhibitory fluoropyrimidine may show superior activity against DPD-high tumours (e. g., tumours treated with oxaliplatin) compared with FOLFIRI. British Journal of Cancer (2012) 107, 1950-1955. doi:10.1038/bjc.2012.502 www.bjcancer.com Published online 20 November 2012 (C) 2012 Cancer Research UK

引用

页码：1950 / 1955

页数：6

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