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130. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

30.04. - 03.05.2013, München

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Identification of a microRNA expression signature for radiochemosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g

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  • Junius Salendo - Universitätsmedizin Göttingen, Klinik für Allgemein und Visceralchirurgie, Göttingen
  • Melanie Spitzner - Universitätsmedizin Göttingen, Klinik für Allgemein und Visceralchirurgie, Göttingen
  • Frank Kramer - Universitätsmedizin Göttingen, Medizinische Statistik, Göttingen
  • Peter Jo - Universitätsmedizin Göttingen, Klinik für Allgemein und Visceralchirurgie, Göttingen
  • Tim Beissbarth - Universitätsmedizin Göttingen, Medizinische Statistik, Göttingen
  • Hendrik Wolff - Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie, Göttingen
  • Heinz Becker - Universitätsmedizin Göttingen, Klinik für Allgemein und Visceralchirurgie, Göttingen
  • Matthias Dobbelstein - Universitätsmedizin Göttingen, Molekulare Onkologie, Göttingen
  • B. Michael Ghadimi - Universitätsmedizin Göttingen, Klinik für Allgemein und Visceralchirurgie, Göttingen
  • Marian Grade - Universitätsmedizin Göttingen, Klinik für Allgemein und Visceralchirurgie, Göttingen
  • Jochen Gaedcke - Universitätsmedizin Göttingen, Klinik für Allgemein und Visceralchirurgie, Göttingen

Deutsche Gesellschaft für Chirurgie. 130. Kongress der Deutschen Gesellschaft für Chirurgie. München, 30.04.-03.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. Doc13dgch660

doi: 10.3205/13dgch660, urn:nbn:de:0183-13dgch6608

Published: April 26, 2013

© 2013 Salendo et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Introduction: Preoperative 5-fluorouracil-based chemoradiotherapy is the standard treatment for locally advanced rectal carcinomas. However, the individual tumor response is very heterogeneous, ranging from complete resistance to regression. Therefore, ascertaining the role of microRNAs (miRNAs) in therapy response as well as identification certain miRNA as predictive markers for response remains very crucial.

Material and methods: Using an in-vitro model of 12 colorectal cancer cell lines, we compare the pretherapeutic miRNA expression profiles of these cell lines with the previously assessed radiochemoresistance of each cell lines, respectively. Differences in treatment sensitivity of the cell lines and miRNAs expression were then correlated. Colony formation assays were used for the functional validation in-vitro. To asses the clinical applicability miRNA expressions of 64 pretherapeutic biopsies from patients with locally advanced cancer treated with 5-FU based RCT were analyzed.

Results: We identified 36 miRNAs whose expression levels correlated significantly with the heterogeneous sensitivity of the cell lines to chemoradiotherapy (p < 0.05). Microarray measurements were independently validated using semi-quantitative real-time PCR. miR-320, miR-132, miR-429, miR-224 and let-7g were then functionally validated in-vitro by transfection of corresponding miRNA mimics. Analysis of miRNA expression in rectal cancer patients biopsies showed high correlation of miR-224 expression with poor prognosis (p=0.043).

Conclusion: We identified 36 miRNAs that associated with response to chemoradiotherapy. Functional validations of miR-320, miR-132, miR-429, miR-224 and let-7g have been undertaken in-vitro underlining the regulatory effects of the specific miRNAs. Further miR-224 found out to be significantly correlated to Disease Free Survival (DFS). An independent prospective validation in a clinical trial will be performed.