title: MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer.
abstract: Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma recurrence. Using macro-dissection followed by quantitative real-time PCR, we measured miR-9, miR-10b, miR-21 and miR-146b expression levels in formalin-fixed, paraffin-embedded samples of 66 patients with papillary thyroid carcinoma categorized into two groups: the recurrent group (n = 19) and the non-recurrent group (n = 47). All patients underwent total thyroidectomy and were followed for at least 120 months after surgery to be considered recurrence-free. Univariate and multivariate analysis were performed using the Cox proportional hazard model in order to identify associations between multiple clinical variables and microRNA expression levels and papillary thyroid carcinoma recurrence. MiR-9 and miR-21 expression levels were found to be significant prognostic factors for recurrence in patients with papillary thyroid carcinoma (HR = 1.48; 95 % CI 1.24-1.77, p < 0.001; and HR = 1.52; 95 % CI 1.18-1.94, p = 0.001; respectively). Multivariate analysis involving the expression level of miR-9 and miR-21 and various clinical parameters identified the expression of these microRNAs as independent prognostic factors for papillary thyroid cancer patients. In conclusion, our results support the potential clinical value of miR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid carcinoma.
authors.affiliation: Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, São Paulo, SP, 05652-000, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Sondermann
authors.forename: Flavia Maziero
authors.initials: FM
authors.lastname: Andreghetto
authors.forename: Ana Carolina Bernardini
authors.initials: AC
authors.lastname: Moulatlet
authors.forename: Elivane
authors.initials: E
authors.lastname: da Silva Victor
authors.forename: Marilia Germanos
authors.initials: MG
authors.lastname: de Castro
authors.forename: Fábio Daumas
authors.initials: FD
authors.lastname: Nunes
authors.forename: Lenine Garcia
authors.initials: LG
authors.lastname: Brandão
authors.forename: Patricia
authors.initials: P
authors.lastname: Severino
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000556:secondary* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D013965:Thyroidectomy; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs