Chapter

The value of survivin gene expression in peripheral blood as a non-invasive prognostic factor in patients with esophageal cancer

Authors:
  • KMG Klinik Silbermühle GmbH
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Abstract

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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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 various gastrointestinal cancers and if they decrease following complete surgical resection. Blood samples from 40 gastrointestinal cancer patients were analyzed prior and following surgical resection by direct quantitative real-time reverse transcriptase-PCR (RT-PCR) assays. Survivin mRNA expression was pre-operatively detected in 35 of 40 cancer patients (88%). Post-operative survivin levels were significantly lower than pre-operative levels in 59% of resected patients and were non-detectable in 38% (Wilcoxon rank test: P < 0.04). This is the first report showing that direct quantitative real-time RT-PCR analysis of survivin mRNA expression in peripheral blood of patients with gastrointestinal cancers is technically feasible. Survivin mRNA levels fall significantly following complete resection and might become a molecular marker for the completeness of surgical resection.
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