Dysregulated MicroRNA Expression in Adenocarcinoma of the Uterine Cervix: Clinical Impact of MiR-363-3p

Objective: Adenocarcinoma (ACA) of the uterine cervix is increasing in incidence and currently accounts for approximately 20% of all cervical malignancies. MicroRNAs (miRNAs) have been investigated as potential biomarkers of cervical cancer; however, their role in ACA remains unknown. Here, we characterized miRNA expression profiles and investigated miRNAs as diagnostic and prognostic factors in ACA.

Methods: Evaluation of genome-wide miRNA expression profiles in ACA by microarray led to the identification of ten candidate miRNAs, whose expression patterns were validated by qRT-PCR in 45 ACA, 10 normal control, and 15 squamous cell carcinoma samples. The association between miRNA expression and prognosis was analyzed in patients with ACA.

Results: Microarray analysis identified 86 miRNAs that were dysregulated more than 2.0-fold (p<0.05) in ACA relative to normal tissues of the uterine cervix. Five most over- and underexpressed miRNAs were selected respectively and their expression patterns were confirmed in the validation set. MiR-135b, miR-192, and miR194 were overexpressed in ACA, and miR-363-3p, miR-195 and miR-199b were significantly associated with conventional prognostic factors. Overexpression of miR-363-3p by more than 2.5-fold relative to the normal control was a strong predictor of favorable prognosis (hazard ratio, 0.1; 95% confidence interval, 0.009-0.779) after adjusting for confounders.

Conclusions: MiR-135b, miR-192, and miR-194 are altered in uterine cervical ACA, and miR-363-3p is an independent favorable prognostic factor in ACA. These miRNAs could be of value as biomarkers for the diagnosis and prognosis of ACA.