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Differential expression of microRNAs in aggressive and non-aggressive papillary thyroid carcinomas

Introduction Papillary thyroid carcinoma is the most common malignancy of the thyroid gland. The usual treatment is surgery, followed by radioactive iodine treatment in advanced cases. Approximately 13% of patients experience local or distant disease. Despite the identification of several risk factors, it is difficult to predict the patients in which metastases is likely to recur. MicroRNAs are short non-coding RNAs that play a central role in the regulation of gene expression by binding to target genes. They are related to various thyroid tumours. The study aimed to evaluate the expression of microRNAs between aggressive and nonaggressive papillary thyroid carcinomas. Materials and methods The computerized database—of Rabin Medical Center—of 10 patients with papillary thyroid carcinoma who underwent treatment and experienced recurrence between 2005 and 2011 was reviewed. They were compared with a control group of 10 patients with similar * Corresponding author Email: nshomron@post.tau.ac.il Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 1 Department of Otorhinolaryngology and Head and Neck Surgery, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Israel; and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 2 Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 3 Department of Pathology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Israel 4 Bioinformatics Unit, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel demographic characteristics who did not experience disease recurrence. Formalin-fixed, paraffin-embedded tissue samples were obtained from all 20 patients. Total RNA was extracted and microRNA expression profiles between the two cohorts were compared. Results and discussion We identified 80 microRNAs with differential expression in papillary thyroid carcinoma when comparing aggressive versus non-aggressive patient samples. Most microRNAs were not described in thyroid cancer. Several of these could be potential biomarkers for future diagnosis, and their identification could possibly be a first step for more effective therapeutics. Conclusion In conclusion, we identified a group of 80 miRNAs that were differently expressed in aggressive and nonaggressive papillary thyroid carcinomas. Expression of miR-4835p was found to be the most significant in terms of aggressive behaviour of papillary thyroid carcinomas. Introduction The incidence of clinically palpable thyroid nodules in the general adult population is 4%–7%; 5% of these nodules are malignant1. Thyroid cancer accounts for 95% of all endocrine malignancies and for approximately 2% of all malignancies2. This prevalence varies across the world and rises in areas of endemic iodine deficiency3. In the last two decades, an increasing incidence of thyroid malignancy has been noted1. This trend could be due to improved clinical diagnosis and not an actual increase in the incidence of malignancy1. The majority of tumours are well differentiated and of follicular cell origin4. The most common thyroid malignancy is papillary thyroid carcinoma, which accounts for approximately 80% of all thyroid cancers5. Papillary thyroid carcinoma carries a good prognosis with a fiveyear survival rate greater than 97%6. The treatment of papillary carcinoma is surgical resection followed by radioactive iodine treatment, which serves to destroy thyroid remnants. External beam radiation is sometimes considered for patients with aggressive disease1. The majority of patients are cured after the initial treatment. Approximately 13% of patients experience an aggressive course, which leads to local, regional and/or distant metastasis7. Recurrence usually occurs months or years after initial treatment1. The major clinicopathological risk factors that are associated with aggressive disease are as follows: patients younger than 20 years, males older than 40 years and females older than 50 years, male gender, prior history of radiation exposure, family history of thyroid malignancy, tumour size >4 cm, extrathyroidal tumour spread, tumour invasion into blood vessels and local and distal metastases8. Several scoring systems have been developed to predict the aggressive course of the disease, with the f o l l o w i n g b e i n g t h e m o s t documented: AMES (patient age, the presence of metastases, extent of tumor invasion, and tumor size); AGES (age at diagnosis, histological