Endocrine Abstracts

Objectives: The specter of malignant thyroid lesions comprises tumors with different degrees of differentiation, rendering the differential diagnosis and prognosis of these tumors challenging. Focal adhesion kinase (FAK) is a tyrosine kinase involved in cellular communication and locomotion, functioning as a hub in the interactome of focal adhesions. Its upregulation has been demonstrated in a number of tumor types including thyroid cancer. FAK is regulated on several levels, one of which includes posttranscriptional inhibition by microRNAs among which are miR-7-5p, miR-135a-5p, and miR-138-5p. Changes in the regulation of FAK can disturb its activation and indirectly influence malignant transformation and cancer progression. We aimed to investigate how the levels of microRNA regulators of FAK correlate with histologic aggressiveness, clinicopathological factors and assess their usefullness in differential diagnostics.

Methods: We collected the samples of postoperative thyroid tumor tissues along with the adjacent normal thyroid gland tissue from 82 patients. We classified the cases into 5 groups with increasing aggressiveness: healthy tissue, follicular and classical variant of papillary thyroid carcinoma (PTC), rare forms of PTC and anaplastic carcinoma. Three microRNAs (miR-7-5p, miR-135a-5p, and miR-138-5p) were selected by literature review and bioinformatic analysis for miR target prediction via miRDB software tool. MiRNA levels were determined via quantitative RT-PCR. TCGA database was queried via UCSC Xena tool, developed by University of California Santa Cruz.

Results: In our sample cohort all three miRs were upregulated in healthy tissue compared to malignant. MiR-135a-5p was negatively correlated with tumor aggressiveness showing a decreasing trend in expression in more aggressive tumor types. The expression of miR-135a-5p and miR-138-5p significantly discriminated follicular from the classical variant of PTC. Neither miR correlated with clinicopathological parameters. The results of TCGA analysis corroborated these findings, and showed that miR135a and miR138 are negatively correlated to the miRNA expression levels of FAK gene.

Conclusions: The selected miRs undergo downregulation during thyroid neoplastic transformation, and could present thyroid tumor suppressors whose effect is exerted through FAK regulation. MiR-135-5p although correlated to histological aggressiveness, does not show prognostic usefulness. MiR-135a-5p, and miR-138-5p are beneficial in thyroid differential diagnostics, while pinpointing the different developmental paths for the different PTC subtypes.