期刊
BRITISH JOURNAL OF CANCER
卷 103, 期 7, 页码 1025-1033出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6605846
关键词
colon cancer; AMPK; ERK; energy balance; prognosis
类别
资金
- US National Institute of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA131945, K07 CA122826]
- Bennett Family Fund
- Entertainment Industry Foundation through National Colorectal Cancer Research Alliance
- Uehara Memorial Foundation
- Japan Society for Promotion of Science
BACKGROUND: AMP-activated protein kinase (AMPK, PRKA) has central roles in cellular metabolic sensing and energy balance homeostasis, and interacts with various pathways (e. g., TP53 (p53), FASN, MTOR and MAPK3/1 (ERK)). AMP-activated protein kinase activation is cytotoxic to cancer cells, supporting AMPK as a tumour suppressor and a potential therapeutic target. However, no study has examined its prognostic role in colorectal cancers. METHODS: Among 718 colon and rectal cancers, phosphorylated AMPK (p-AMPK) and p-MAPK3/1 expression was detected in 409 and 202 tumours, respectively, by immunohistochemistry. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical and tumoral features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF and PIK3CA mutations. RESULTS: Phosphorylated AMPK expression was not associated with survival among all patients. Notably, prognostic effect of p-AMPK significantly differed by p-MAPK3/1 status (P(interaction) = 0.0017). Phosphorylated AMPK expression was associated with superior colorectal cancer-specific survival (adjusted HR 0.42; 95% confidence interval (CI), 0.24-0.74) among p-MAPK3/1-positive cases, but not among p-MAPK3/1-negative cases (adjusted HR 1.22; 95% CI: 0.85-1.75). CONCLUSION: Phosphorylated AMPK expression in colorectal cancer is associated with superior prognosis among p-MAPK3/1-positive cases, but not among p-MAPK3/1-negative cases, suggesting a possible interaction between the AMPK and MAPK pathways influencing tumour behaviour. British Journal of Cancer (2010) 103, 1025-1033. doi:10.1038/sj.bjc.6605846 www.bjcancer.com Published online 31 August 2010 (C) 2010 Cancer Research UK
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