Max Michael Traeger1, Jan Rehkaemper2, Hansjoerg Ullerich3, Konrad Steinestel2, Eva Wardelmann2, Norbert Senninger1, Sameer Abdallah Dhayat4. 1. Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany. 2. Gerhard-Domagk-Institute of Pathology, University of Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany. 3. Department of Medicine B, Gastroenterology and Hepatology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany. 4. Department of General, Visceral and Transplantation Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany. Sameer.dhayat@ukmuenster.de.
Abstract
PURPOSE: Early treatment of pancreatic ductal adenocarcinoma (PDAC) is significantly delayed due to the lack of liquid biopsy markers for early diagnosis at surgically resectable tumor stages. Recent studies suggest that microRNA-205 (miR-205) is involved in PDAC progression by post-transcriptional regulation of epithelial-to-mesenchymal transition (EMT). However, the clinical potential of miR-205 as diagnostic and prognostic marker remains undefined and its exact role in PDAC is still ambiguous. This retrospective study is a substantial contribution to this on-going scientific discussion. METHODS: Expression analysis of miR-205 and its molecular targets in PDAC cell lines (n = 5), human tissue (n = 73), and blood serum samples (n = 85) by qRT-PCR, tissue microarray immunohistochemistry, and western blot. Descriptive and explorative statistical analysis of miR-205's clinical potential for diagnosis and prognosis of PDAC. RESULTS: The expression of miR-205 differs more than 2000-fold (p < 0.001) between epithelial and mesenchymal-like human PDAC cell lines correlating with EMT-marker expression of E-cadherin, vimentin, fibronectin, and ZEB-1. Expression of miR-205 is significantly upregulated in carcinoma tissue (eightfold, p = 0.028) and serum (2.3-fold, p = 0.023) of PDAC patients compared to age-matched healthy controls. In our patient collective circulating miR-205 in combination with CA.19-9 outperforms the diagnostic accuracy of CA.19-9 alone with an AUC of 0.890 (p < 0.001), sensitivity of 0.867, and specificity of 0.933. Though non-significant, low expression of circulating miR-205 is more frequent in advanced tumor stages combined with a worse overall survival (6.9 vs. 11.9 months, p = 0.176). CONCLUSION: Besides its controversial role in carcinogenesis, miR-205 shows high potential as a solid and liquid biopsy marker in PDAC. This result is an urgent call for larger confirmatory multi-center studies.
PURPOSE: Early treatment of pancreatic ductal adenocarcinoma (PDAC) is significantly delayed due to the lack of liquid biopsy markers for early diagnosis at surgically resectable tumor stages. Recent studies suggest that microRNA-205 (miR-205) is involved in PDAC progression by post-transcriptional regulation of epithelial-to-mesenchymal transition (EMT). However, the clinical potential of miR-205 as diagnostic and prognostic marker remains undefined and its exact role in PDAC is still ambiguous. This retrospective study is a substantial contribution to this on-going scientific discussion. METHODS: Expression analysis of miR-205 and its molecular targets in PDAC cell lines (n = 5), human tissue (n = 73), and blood serum samples (n = 85) by qRT-PCR, tissue microarray immunohistochemistry, and western blot. Descriptive and explorative statistical analysis of miR-205's clinical potential for diagnosis and prognosis of PDAC. RESULTS: The expression of miR-205 differs more than 2000-fold (p < 0.001) between epithelial and mesenchymal-like human PDAC cell lines correlating with EMT-marker expression of E-cadherin, vimentin, fibronectin, and ZEB-1. Expression of miR-205 is significantly upregulated in carcinoma tissue (eightfold, p = 0.028) and serum (2.3-fold, p = 0.023) of PDAC patients compared to age-matched healthy controls. In our patient collective circulating miR-205 in combination with CA.19-9 outperforms the diagnostic accuracy of CA.19-9 alone with an AUC of 0.890 (p < 0.001), sensitivity of 0.867, and specificity of 0.933. Though non-significant, low expression of circulating miR-205 is more frequent in advanced tumor stages combined with a worse overall survival (6.9 vs. 11.9 months, p = 0.176). CONCLUSION: Besides its controversial role in carcinogenesis, miR-205 shows high potential as a solid and liquid biopsy marker in PDAC. This result is an urgent call for larger confirmatory multi-center studies.
Authors: Dan Calatayud; Christian Dehlendorff; Mogens K Boisen; Jane Preuss Hasselby; Nicolai Aagaard Schultz; Jens Werner; Heike Immervoll; Anders Molven; Carsten Palnæs Hansen; Julia S Johansen Journal: Biomark Res Date: 2017-02-21