Survivin Gene Expression in Blood As a Prognostic Marker in the Surgical Therapy of Patients with Esophageal Cancer
Daniel Vallbohmer*1, Andreas C. Hoffmann1,2, Peter Grimminger1, Frederike C. Ling1, Ralf Metzger1, Paul M. Schneider1,3, Arnulf H. HöLscher1, Jan Brabender1
1Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany; 2Department of Internal Medicine, University of Duisburg-Essen, Essen, Germany; 3Department of Visceral and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland
Background : Although circulating tumor DNA has been detected in patients with different types of cancer, less is known about free RNA in cancer patients. Therefore, we evaluated if mRNA expression of survivin, an inhibitor of apoptosis, can be used to detect circulating tumor cells in peripheral blood of patients with esophageal cancer. Furthermore, we assessed the influence of complete surgical resection and the association of survivin levels in peripheral blood with prognosis.Methods: Sixty-two patients (53 men, 9 women; median age 60 years) with esophageal cancer (adenocarcinoma: n=37; squamous cell cancer: n=25) scheduled for surgical resection were included. A neoadjuvant radiochemotherapy was performed in 24 (39%) patients. Whole blood was drawn one day pre- and 10 days postoperatively from all study patients. After extraction of cellular tumor-RNA from blood samples, quantitative expression analysis of survivin was done by real-time reverse transcription polymerase chain reaction.Results: Survivin expression in blood was detectable in 81 % of the study patients. The pre- and postoperative mRNA amount of survivin did not differ between patients with adenocarcinoma and squamous cell cancer (p=0.26). Postoperative survivin expression levels were significantly lower than preoperative levels (p=0.02). With a median overall survival of 29.4 months, patients with a preoperative survivin expression above the 60th percentile had a significant shorter overall survival than patients with a reduced expression profile (p=0.03; 23 vs. 38 months).Conclusions: Direct quantification of survivin mRNA expression in peripheral blood of patients with esophageal cancer is technically feasible and is significantly reduced by complete surgical resection. Moreover, survivin gene expression in blood might become a non-invasive prognostic molecular marker in patients with esophageal cancer.
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