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Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence.

Sjoerd H den Uil ,
Veerle M H Coupé ,
Janneke F Linnekamp ,
Evert van den Broek ,
Jeroen A C M Goos ,
Pien M Delis-van Diemen ,
Eric J Th Belt ,
Nicole C T van Grieken ,
Patricia M Scott ,
Louis Vermeulen ,
Jan Paul Medema ,
Herman Bril ,
Hein B A C Stockmann ,
Robert T Cormier ,
Gerrit A Meijer ,
Remond J A Fijneman

Abstract

METHODS

KCNQ1 mRNA expression was assessed in 90 stage II colon cancer patients (AMC-AJCCII-90) using microarray gene expression data. Subsequently, KCNQ1 protein expression was evaluated in an independent cohort of 386 stage II and stage III colon cancer patients by immunohistochemistry of tissue microarrays.

CONCLUSIONS

We conclude that KCNQ1 is a promising biomarker for prediction of disease recurrence and may aid stratification of patients with stage II MSS colon cancer for adjuvant chemotherapy.

RESULTS

Low KCNQ1 mRNA expression in stage II microsatellite stable (MSS) colon cancers was associated with poor disease-free survival (DFS) (P=0.025). Loss of KCNQ1 protein expression from epithelial cells was strongly associated with poor DFS in stage II MSS (P<0.0001), stage III MSS (P=0.0001) and stage III microsatellite instable colon cancers (P=0.041). KCNQ1 seemed an independent prognostic value in addition to other high-risk parameters like angio-invasion, nodal stage and microsatellite instability-status.

BACKGROUND

Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at risk for recurrence is an unmet clinical need. KCNQ1 was previously identified as a tumour suppressor gene and loss of expression was associated with poor survival in patients with CRC liver metastases. In this study the prognostic value of KCNQ1 in stage II and stage III colon cancer patients was examined.

More about this publication

British journal of cancer

Volume 115
Issue nr. 12
Pages 1565-1574
Publication date 06-12-2016

Full text links

Publisher website (DOI) 10.1038/bjc.2016.376
Europe PubMed Central 27855440
Pubmed 27855440

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