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Open Access Research

MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients

Marek Svoboda125*, Jiri Sana15, Pavel Fabian3, Ilona Kocakova1, Jana Gombosova4, Jana Nekvindova6, Lenka Radova7, Rostislav Vyzula1 and Ondrej Slaby15

Author Affiliations

1 Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 656 53, Czech Republic

2 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic

3 Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic

4 Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic

5 Central European Institute of Technology, Masaryk University, Kamenice 5, Brno, Czech Republic

6 Institute of Clinical Biochemistry and Diagnostics, Faculty of Medicine and Faculty Hospital in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic

7 Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and Palacky University affiliated Hospital, Olomouc, Czech Republic

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Radiation Oncology 2012, 7:195  doi:10.1186/1748-717X-7-195

Published: 20 November 2012

Abstract

Background

Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5-fluorouracil) followed by radical surgical resection. Unfortunately, a significant proportion of tumors do not respond enough to the neoadjuvant treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers for rectal cancer patients.

Methods

We selected 20 patients who underwent neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were classified as most sensitive or resistant to the treatment. These two groups were compared using large-scale miRNA expression profiling.

Results

Expression levels of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR-29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been correctly classified.

Conclusions

Our pilot study suggests that miRNAs are part of the mechanisms that are involved in response of rectal cancer to the chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p and let-7e), the connection between their expression and radioresistance or chemoresistance to inhibitors of thymidylate synthetase was already established.

Keywords:
Rectal cancer; microRNA; Prediction; Neoadjuvant chemoradiotherapy; Radiation; Capecitabine; 5-fluorouracil; Thymidylate synthetase