Prognostic Significance of Survivin Expression and Combined Analysis with Cancer Stem Cell and Epithelial-Mesenchymal Transition-related Markers in Patients with Rectal Cancer Undergoing Preoperative Chemoradiotherapy

Aim To identify the candidate marker predicting treatment response and survival outcome in rectal cancer patients who received preoperative chemoradiotherapy (CRT). Patients and methods Between 2000 and 2015, 159 patients with histologically-confirmed rectal adenocarcinoma underwent preoperative CRT followed by surgery. Among them, 70 patients were enrolled and the expression of survivin, cancer stem cell markers (CD44 and CD133) and epithelial-mesenchymal transition markers (E-cadherin and TWIST1) in pretreatment biopsy specimens were evaluated by immunohistochemistry. Associations between the expression of markers and clinical outcomes were evaluated. Results The median follow-up period of all patients was 71 (range=15-203) months. Five-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRRFS) and distant metastasis-free (DMFS) survival were 80.5%, 60.2% 90.1% and 76.5%, respectively. A significant association between survivin overexpression and worse treatment outcome was shown on univariate analyses for OS, DFS and DMFS (p=0.022, 0.002, and 0.005, respectively). On multivariate analysis, survivin overexpression was an adverse prognosticator for DFS and DMFS (p=0.007 and 0.015, respectively), with a borderline significant trend towards a shorter OS (p=0.069). Four other single biomarkers were not associated with survival outcomes. However, overexpression of both survivin and CD44 was significantly associated with worse OS on multivariate analysis (p=0.003). Conclusion Survivin combined with CD44 might be a candidate biomarker for the prediction of recurrence and survival in patients who received preoperative CRT for rectal cancer. Further research with a larger population is needed to validate these results.