Abstract 1942: Identification of a microRNA expression signature for radiochemosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g

Autor: Heinz Becker, Mathias Dobbelstein, Melanie Spitzner, Peter Jo, Michael Ghadimi, Tim Beissbarth, Marian Grade, Jochen Gaedcke, Junius Salendo, Hendrik Wolff, Frank Kramer
Rok vydání: 2013
Předmět:
Zdroj: Cancer Research. 73:1942-1942
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2013-1942
Popis: Background: 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. Materials/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 in two independent cell lines 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. Citation Format: Junius Salendo, Melanie Spitzner, Frank Kramer, Peter Jo, Tim Beissbarth, Hendrik A. Wolff, Heinz Becker, Mathias Dobbelstein, Michael Ghadimi, Marian Grade, Jochen Gaedcke. Identification of a microRNA expression signature for radiochemosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1942. doi:10.1158/1538-7445.AM2013-1942
Databáze: OpenAIRE
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