Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer
- Author(s)
- Jorissen, RN; Christie, M; Mouradov, D; Sakthianandeswaren, A; Li, S; Love, C; Xu, ZZ; Molloy, PL; Jones, IT; McLaughlin, S; Ward, RL; Hawkins, NJ; Ruszkiewicz, AR; Moore, J; Burgess, AW; Busam, D; Zhao, Q; Strausberg, RL; Lipton, L; Desai, J; Gibbs, P; Sieber, OM;
- Journal Title
- Br J Cancer
- Publication Type
- Journal Article
- Abstract
- BACKGROUND: APC mutations (APC-mt) occur in approximately 70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. METHODS: APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort. RESULTS: Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR1.79, P0.015; RFS HR1.88, P0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt-like signature MSS cases showed poorer survival than APC-mt-like signature MSS or MSI cases (OS HR2.50, P0.010; RFS HR2.14, P0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P0.016). CONCLUSIONS: APC-wt status is a marker of poor prognosis in MSS proximal colon cancer.British Journal of Cancer advance online publication 25 August 2015; doi:10.1038/bjc.2015.296 www.bjcancer.com.
- Publisher
- NPG
- Research Division(s)
- Systems Biology And Personalised Medicine; Structural Biology
- PubMed ID
- 26305864
- Link To PubMed Central Version
- https://www-ncbi-nlm-nih-gov/pmc/articles/PMC4578087/
- Publisher's Version
- https://doi.org/10.1038/bjc.2015.296
- Open Access at Publisher's Site
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Creation Date: 2015-09-01 03:55:19
Last Modified: 2018-03-16 02:28:09