Identifying patients with an unfavorable prognosis in early stages of colorectal carcinoma
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Alexander Hendricks1, Greta-Lou Eggebrecht1, Alexander Bernsmeier1, Reinhild Geisen2, Katharina Dall1, Anna Trauzold2, Thomas Becker1, Holger Kalthoff2, Clemens Schafmayer1, Christian Röder2 and Sebastian Hinz1
1Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
2Institute for Experimental Cancer Research, Christian-Albrechts University, Kiel, Germany
Sebastian Hinz, email: [email protected]
Keywords: colorectal cancer; liquid biopsy; circulating tumor cells; cytokeratin 20; prognostic marker
Received: December 15, 2017 Accepted: April 24, 2018 Published: June 08, 2018
Background: In recent years, the concept of liquid biopsy diagnostics in detection and progress monitoring of malignant diseases gained significant awareness. We here report on a semi-quantitative real-time cytokeratin 20 RT-PCR-based assay, for detecting circulating tumor cells within a fraction of peripheral blood mononuclear cells in colorectal cancer patients.
Methods: In total, 381 patients were included. Prior to surgical tumor resection, a peripheral blood sample was drawn. Mononuclear cells were isolated by Ficoll centrifugation and a cytokeratin 20 qRT-PCR assay was performed. Quantitative PCR data was assessed regarding histopathological characteristics and patients´ clinical outcome.
Results: A cut-off value was determined at ≥ 2.77 [EU]. Stratifying patients by this cut-off, it represents a statistically highly significant prognostic marker for both the overall and disease-free survival in the entire cohort UICC I-IV (both p<0.001) and in early tumor stages UICC I+II (overall survival p=0.003 and disease-free survival p=0.005). In multivariate analysis, the cut-off value stands for an independent predictor of significantly worse overall and disease-free survival (p=0.035 and p=0.047, respectively).
Conclusion: We successfully established a highly sensitive real-time qRT-PCR assay by which we are able to identify colorectal cancer patients at risk for an unfavorable prognosis in UICC I and II stages.
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