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 Otorhinolaryngology Head and Neck Surgery and Audiology Rigshospitalet Copenhagen 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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