Synergic effects of cancer stem cells markers, CD44 and embryonic stem cell transcription factor Nanog, on bladder cancer prognosis

Background: Therapy that targets cancer stem cells has the potential to eradicate cancer and prevent tumour recurrence. Therefore, we hypothesized the combined prognostic significance of stem cell markers CD44 (prevalent in basal layer of urothelial carcinoma) and Nanog (embryonic stem cell transcription factor) in bladder cancer. Material and Methods: CD44 and Nanog expression were determined by immunohistochemistry in 112 bladder cancer cases of which 79 were non-muscle invasive and 33 muscle invasive. Results: A significant correlation was found between CD44 and Nanog expression (r = 0.41, p < 0.001). The bladder cancer patients with high CD44 and Nanog expression had poor recurrence-free survival and poor overall survival (all p < 0.01). Multivariate Cox regression analysis identified lymph node positivity (hazard ratio; HR 3.81, 95% confidence interval; CI 1.66-8.75), CD44 (HR/95%CI 7.03 [3.04-16.22]) and Nanog (HR/95%CI 2.89 [1.23-6.77]) as independent prognostic biomarkers for recurrence-free survival, whilst a combined index of CD44 and Nanog expression (high expression group; HR/95%CI 25.45 [6.71-96.50] for recurrence-free survival) and lymph node positivity (HR/95%CI 3.68 [1.63-8.33] for recurrence-free survival) were independent prognostic biomarkers for recurrence-free survival and overall survival (all p < 0.001). Conclusions: A combined index of CD44 and Nanog expression is a promising prognostic predictor of recurrence-free survival and overall survival in bladder cancer. It may help identification of patients who will benefit from intensive treatment.