Papillary Thyroid Carcinoma Tissue miR-146b, -21, -221, -222, -181b Expression in Relation with Clinicopathological Features.

Aistė Kondrotienė,Rytis Stakaitis,Ieva Golubickaitė,Mintautė Kazokaitė,Rasa Verkauskienė,Vaida Simanavičienė,Dalia Daukšienė,Valdas Šarauskas,Aurelija Žvirblienė,Daina Pamedytytė,Birutė Žilaitienė,Albertas Daukša,Raimonda Klimaitė

doi:10.3390/diagnostics11030418

Aistė Kondrotienė, Rytis Stakaitis + Show 11 more

Open Access

https://doi.org/10.3390/diagnostics11030418

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Abstract

We analyzed miR-146b, miR-21, miR-221, miR-21, and miR-181b in formalin fixed paraffin-embedded papillary thyroid carcinoma (PTC) tissue samples of 312 individuals and evaluated their expression relationship with clinicopathological parameters. A higher expression of miR-21 was related to unifocal lesions (p < 0.011) and autoimmune thyroiditis (0.007). miR-221, miR-222 expression was higher in the PTC tissue samples with extrathyroidal extension (p = 0.049, 0.003, respectively). In a group of PTC patients with pT1a and pT1b sized tumors, the expression of miR-146b, miR-21, miR-221, and miR-222 in PTC tissue samples was lower than in patients with pT2, pT3, and pT4 (p = 0.032; 0.0044; 0.003; 0.001; 0.001, respectively). Patients with lymph node metastases had higher expression of miR-21, -221, -222, and -181b (p < 0.05). A high expression of miR-146b, miR-21, miR-221 panel was associated with decreased overall survival (OS) (Log rank p = 0.019). Univariate analysis revealed that presence of metastatic lymph nodes and high expression of miR-146b, miR-21, and miR-221 panels were associated with increased hazard of shorter OS. After multivariate analysis, only sex (male) and age (≥55 years) emerged as independent prognostic factors associated with shorter OS (HR 0.28 (95% CI 0.09–0.86) and HR 0.05 (95% CI 0.01–0.22), respectively). In conclusion, 5 analyzed miRs expression have significant relations to clinicopathologic parameters so further investigations of these molecules are expedient while searching for prognostic PTC biomarkers.

Highlights

Epigenetic biomarkers combined with clinicopathologic features of papillary thyroid carcinoma (PTC) might be beneficial in PTC patients risk stratification processes [10,32]
Five miRs (-146b, -21, -221, -222, and -181b) were selected for this study based on previous reports showing potential of these molecules in identifying and risk stratifying PTC patients [14,15,16,17,18,19,20,21,22,37]
According to The Cancer Genome Atlas (TCGA) analysis and previous studies, miR-146b, -21, -221, -222, -181b have higher expression levels in PTC compared to healthy thyroid tissue or nodular goiter [14,15,16,17,18,19,20,21,22,33]

Summary

Introduction

According to the European Network of Cancer. Registries, in Europe an estimated 53,000 thyroid cancer cases were newly diagnosed in. 6300 Europeans were estimated to have died of thyroid cancer [2]. The highest estimated age-standardized incidence ratio in Europe is recorded in Lithuania (15.5 cases per 100,000 person-years) [2]. The ten-year survival rate is usually higher than 80–90% for a patient with PTC after indicated treatment [2,3]. Local regional recurrences occur in up to 30% of patients with PTC [4]. Managed patients result in potentially higher fatal outcomes due to the lack of sufficient prognostic data/markers, inadequate periodic individualized follow-up risk assessments, and/or insufficient initial treatment [5]

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