Overexpression of miR-21-5p as a predictive marker for complete tumor regression to neoadjuvant chemoradiotherapy in rectal cancer patients.
BMC Med Genomics
; 7: 68, 2014 Dec 11.
Article
en En
| MEDLINE
| ID: mdl-25496125
ABSTRACT
BACKGROUND:
Neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery is the preferred treatment strategy for locally advanced rectal cancer. However, complete tumor regression is observed in a significant proportion of patients after nCRT, making them ideal candidates for alternative treatment strategies to this considerably morbid procedure. Identification of such patients based on clinical findings (complete clinical response - cCR) is difficult mainly because it relies on subjective clinical and imaging studies. Our goal was to identify biomarkers capable of predicting complete response to nCRT.METHODS:
We analyzed miRNA expression profile using deep sequencing in rectal tumor biopsies prior to nCRT. Differential expression was investigated by EdgeR for a training (n = 27) and a validation (n = 16) set of patients to identify miRNAs associated with treatment response (complete vs. incomplete). In vitro experiments with two cancer cell lines were also performed in order to evaluate the possible role of miRNAs on response to nCRT.RESULTS:
We found 4 miRNAs differentially expressed between complete and incomplete responders to nCRT. In addition, validation was performed using an independent group of patients and miR-21-5p was confirmed as being overexpressed in complete responders. Overall sensitivity and specificity of miR-21-5p expression in predicting complete response to nCRT was 78% and 86% respectively. Interestingly, in a subset of patients with cCR followed by early local recurrence, the expression level of miR-21-5p was considerably low, similarly to incomplete responders. We also found SATB1, a miR-21-5p target gene and known multidrug resistance gene, whose expression was inversely correlated with miR-21-5p expression. Finally, we performed functional experiments and showed that miR-21-5p and SATB1 may be directly involved with poor response to nCRT in rectal cancer patients.CONCLUSIONS:
This study suggests miR-21-5p as a promising predictive biomarker, which should aid in the selection of patients with cCR to nCRT that potentially could be spared from radical surgery.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias del Recto
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Protocolos de Quimioterapia Combinada Antineoplásica
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Biomarcadores de Tumor
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Terapia Neoadyuvante
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MicroARNs
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Quimioradioterapia
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Recurrencia Local de Neoplasia
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
BMC Med Genomics
Asunto de la revista:
GENETICA MEDICA
Año:
2014
Tipo del documento:
Article