Microarray analysis and functional studies in a novel human colon cancer model of EMT: TAF12 regulates E-cadherin and Fra-1 regulates Vimentin expression

Abstract

Current staging classifications in colorectal cancer are not able to accurately predict patient outcome, and the need for novel prognostic markers is evident. S100A4 is a Ca2+-binding protein which promotes metastasis in several tumour types, and the aim of the present study was to investigate the prognostic impact of S100A4 expression in colorectal cancer. Two hundred and forty two patients with curatively resected adenocarcinoma of the colon or rectum were prospectively included in the study at the time of surgery. S100A4 expression was analysed by immunohistochemistry, and associations with clinicopathological variables and patient outcome were investigated. Nuclear expression of S100A4 was observed in 29% and cytoplasmic expression was observed in 64% of the tumours. In univariate analysis, nuclear S100A4 was a negative predictor of metastasis-free (P = 0.006) and overall survival (P = 0.01), whereas cytoplasmic S100A4 was not associated with patient outcome. In multivariate analysis, nuclear localisation was inversely associated with metastasis-free (P = 0.03) and overall survival (P = 0.02). Interestingly, the prognostic impact was largely confined to TNM stage II, and stage II patients with tumours expressing nuclear S100A4 had a similar prognosis as stage III patients. In conclusion, nuclear expression of S100A4 is a novel prognostic marker in colorectal cancer, and the prognostic value in TNM stage II suggests that nuclear S100A4 could be used in the stratification of stage II patients for adjuvant treatment.