MicroRNA dysregulation in adenoid cystic carcinoma of the salivary gland in relation to prognosis and gene fusion status: a cohort study
Language English Country Germany Media print-electronic
Document type Journal Article
PubMed
30069755
DOI
10.1007/s00428-018-2423-0
PII: 10.1007/s00428-018-2423-0
Knihovny.cz E-resources
- Keywords
- Adenoid cystic carcinoma, MYB, MYBL1, Prognosis, Salivary gland, microRNA,
- MeSH
- Carcinoma, Adenoid Cystic genetics mortality pathology MeSH
- Adult MeSH
- Gene Fusion * MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs analysis MeSH
- Adolescent MeSH
- Young Adult MeSH
- Salivary Gland Neoplasms genetics mortality pathology MeSH
- Prognosis MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- MicroRNAs MeSH
Adenoid cystic carcinoma (ACC) is among the most frequent malignancies of the salivary gland, and is notorious for its prolonged clinical course characterized by frequent recurrences often years after initial treatment. No molecular marker has been shown to have independent prognostic value in ACC, including characteristic gene fusions involving MYB, MYBL1, and NFIB. MicroRNA has been shown to be associated with clinical outcome in numerous malignancies, including one study of ACC, warranting further validation of this class of markers in this disease. Here, we investigate the prognostic value of microRNA in two ACC cohorts: a training cohort (n = 64) and a validation cohort (n = 120) with microarray and qPCR. In the training cohort, multivariate analysis of microarray data found high expression of hsa-miR-6835-3p to be associated with reduced recurrence-free survival (RFS) (p = 0.016). Measuring the highest ranking microRNAs identified in survival analysis in the same cohort, qPCR identified high expression of hsa-miR-4676 to be associated with reduced overall survival (OS) and high expression of hsa-mir-1180 to be associated with improved RFS. This was not confirmed in the validation cohort, in which qPCR identified high expression of hsa-mir-21, hsa-mir-181a-2, and hsa-mir-152 to be associated with reduced OS and high expression of hsa-miR-374c to be associated with improved RFS. Interestingly, two distinct subsets of ACC separated in microRNA expression irrespective of gene fusion status, but without significant difference in outcome. Collectively, qPCR identified several microRNAs associated with OS and RFS, and different subsets of ACC separated according to microRNA expression, suggestive of ACC being a heterogeneous group of malignancies in its microRNA profile.
Bioptic Laboratory Ltd Molecular Pathology Laboratory Pilsen Czech Republic
Department of Ophthalmology Rigshospitalet Glostrup Copenhagen Denmark
Department of ORL Head and Neck Surgery Odense University Hospital Odense Denmark
Department of Otorhinolaryngology and Maxillofacial Surgery Zealand University Hospital Køge Denmark
Department of Pathology Aalborg University Hospital Aalborg Denmark
Department of Pathology Aarhus University Hospital Aarhus Denmark
Department of Pathology Charles University Prague Faculty of Medicine Pilsen Czech Republic
Department of Pathology Herlev Hospital University of Copenhagen Herlev Denmark
Department of Pathology Odense University Hospital Odense Denmark
Department of Pathology Rigshospitalet Copenhagen Denmark
Department of Pathology Zealand University Hospital Roskilde Denmark
Genomic Medicine Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Unit of Human Genetics Department of Clinical Research University of Southern Denmark Odense Denmark
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