Expression profile of miR-17/92 cluster is predictive of treatment response in rectal cancer
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30277504
DOI
10.1093/carcin/bgy100
PII: 5113435
Knihovny.cz E-resources
- MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Biomarkers, Tumor genetics MeSH
- Cell Line, Tumor MeSH
- Rectal Neoplasms drug therapy genetics mortality MeSH
- Cell Proliferation genetics MeSH
- Antineoplastic Agents therapeutic use MeSH
- Gene Expression Regulation, Neoplastic genetics MeSH
- Gene Expression Profiling MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN106 microRNA, human MeSH Browser
- MIRN17 microRNA, human MeSH Browser
- MIRN18 microRNA, human MeSH Browser
- MIRN19A microRNA, human MeSH Browser
- MIRN20a microRNA, human MeSH Browser
- MIRN92 microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
- Antineoplastic Agents MeSH
MicroRNA (miRNA) profiling represents a promising source of cancer-related biomarkers. miRNA signatures are specific for each cancer type and subgroups of patients with diverse treatment sensitivity. Yet this miRNA potential has not been satisfactorily explored in rectal cancer (RC). The aim of the study was to identify the specific miRNA signature with clinical and therapeutic relevance for RC. Expressions of 2555 miRNA were examined in 20 pairs of rectal tumors and matched non-malignant tissues by 3D-Gene Toray microarray. Candidate miRNAs were validated in an independent cohort of 100 paired rectal tissues and in whole plasma and exosomes of 100 RC patients. To study the association of miRNA profile with therapeutic outcomes, plasma samples were taken repeatedly over a time period of 1 year reflecting thus patients' treatment responses. Finally, the most prominent miRNAs were investigated in vitro for their involvement in cell growth. We identified RC-specific miRNA signature that distinguishes responders from non-responders to adjuvant chemotherapy. A predominant part of identified miRNAs was represented by the members of miR-17/92 cluster. Upregulation of miRNA-17, -18a, -18b, -19a, -19b, -20a, -20b and -106a in tumor was associated with higher risk of tumor relapse and their overexpression in RC cell lines stimulated cellular proliferation. Examination of these miRNAs in plasma exosomes showed that their levels differed between RC patients and healthy controls and correlated with patient's treatment response. miRNAs from miR-17/92 cluster represent a non-invasive biomarker to predict posttreatment prognosis in RC patients.
Biomedical Centre Faculty of Medicine in Pilsen Charles University Prague Pilsen Czech Republic
Department of Surgery General University Hospital Prague Czech Republic
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