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Journal of Cancer Research and Clinical Oncology

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22.09.2018 | Original Article – Cancer Research

The ambiguous role of microRNA-205 and its clinical potential in pancreatic ductal adenocarcinoma

verfasst von: Max Michael Traeger, Jan Rehkaemper, Hansjoerg Ullerich, Konrad Steinestel, Eva Wardelmann, Norbert Senninger, Sameer Abdallah Dhayat

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 12/2018

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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.

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Titel: The ambiguous role of microRNA-205 and its clinical potential in pancreatic ductal adenocarcinoma
verfasst von: Max Michael Traeger
Jan Rehkaemper
Hansjoerg Ullerich
Konrad Steinestel
Eva Wardelmann
Norbert Senninger
Sameer Abdallah Dhayat
Publikationsdatum: 22.09.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 12/2018
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-018-2755-9

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The ambiguous role of microRNA-205 and its clinical potential in pancreatic ductal adenocarcinoma

Abstract

Purpose

Methods

Results

Conclusion

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