MicroRNA profiling predicts positive nodal status in papillary thyroid carcinoma in the preoperative setting

Abstract

BACKGROUND The molecular characterization of thyroid nodules in cytological samples has so far been focused on discriminating between benign and malignant forms in a purely diagnostic setting. The evidence on the impact of molecular biomarkers to determine the risk of aggressiveness in cytologically “neoplastic” lesions is limited to genomic alterations (such as BRAF and TERT mutations). The aim of our study was to assess the preoperative role of microRNAs (miRNAs) in predicting the nodal status of patients with papillary thyroid cancer. METHODS A pilot series of histological samples of papillary thyroid carcinoma with (6 cases) or without (6 cases) lymph node metastases, matched for other major clinical and pathological features, was analyzed for global miRNA expression in a screening phase. A set of miRNAs was then validated in a series of 63 consecutive cytological samples of papillary carcinomas: 48 pN‐negative and 15 pN‐positive at histology. RESULTS Unsupervised cluster analysis segregated surgical pN‐negative and pN‐positive samples, except for 1 case. The 45 differentially expressed miRNAs in pN‐positive versus pN‐negative cases were predicted to regulate a wide range of cellular pathways, enriched for Wnt, gonadotropin‐releasing hormone receptor, and cerulein/cholecystokinin receptor signaling. In agreement with their profiles in surgical samples, 4 miRNAs of the 10 selected for validation (miR‐154‐3p, miR‐299‐5p, miR‐376a‐3p, and miR‐302E) had a significant differential expression in cytological samples of papillary carcinoma with lymph node metastases and predicted the positive nodal status with a relatively good performance. CONCLUSIONS MiRNA profiling is a potential promising strategy to define papillary carcinoma aggressiveness in the preoperative setting. ;

Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas

“…In our study, the first reference for the selection of the miRNAs was the study of Nikiforova (2008) [ 28 ] and an additional search on works related to our four selected miRNAs [ 28 , 29 , 30 , 31 , 32 , 33 ], in particular the work by Castagna (2019) [ 29 ], who selected the same miRs in fine-needle aspiration cytology.…”

“…These miRNAs overexpressed were associated with tumor aggressiveness, extra thyroidal extension, recurrence, and metastases, constituting a specific signature of PTC [ 30 ]. The evaluation of miRNA expression may be helpful in the precocious diagnosis and in the evaluation of the biological behavior of PTC [ 31 , 32 , 33 ].…”

“…In our study, the first reference for the selection of the miRNAs was the study of Nikiforova (2008) [28] and an additional search on works related to our four selected miRNAs [28][29][30][31][32][33], in particular the work by Castagna (2019) [29], who selected the same miRs in fine-needle aspiration cytology. Nikiforova et al [28] showed the biological significance and interest of miRNAs analysis in normal and hyperplastic thyroid tissue, estimating that 32% of miRNAs are upregulated and 38% are downregulated in thyroid tumors.…”