TY - JOUR
T1 - Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence
AU - den Uil, Sjoerd H.
AU - Coupé, Veerle M. H.
AU - Linnekamp, Janneke F.
AU - van den Broek, Evert
AU - Goos, Jeroen A. C. M.
AU - Delis-van Diemen, Pien M.
AU - Belt, Eric J. Th
AU - van Grieken, Nicole C. T.
AU - Scott, Patricia M.
AU - Vermeulen, Louis
AU - Medema, Jan Paul
AU - Bril, Herman
AU - Stockmann, Hein B. A. C.
AU - Cormier, Robert T.
AU - Meijer, Gerrit A.
AU - Fijneman, Remond J. A.
PY - 2016/12/6
Y1 - 2016/12/6
N2 - 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. 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. 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. 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
AB - 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. 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. 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. 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
U2 - https://doi.org/10.1038/bjc.2016.376
DO - https://doi.org/10.1038/bjc.2016.376
M3 - Article
C2 - 27855440
SN - 0007-0920
VL - 115
SP - 1565
EP - 1574
JO - British journal of cancer
JF - British journal of cancer
IS - 12
ER -