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Differences in miRNA expression profiles between wild-type and mutated NIFTPs.

Maria Denaro1, Clara Ugolini2, Anello Marcello Poma1

  • 1Department of Surgical PathologyMedical, Molecular and Critical Area, University of Pisa, Pisa, Italy.

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Summary

MicroRNA (miRNA) expression profiles differentiate noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) based on mutation status. Mutated NIFTPs show an invasive-like miRNA profile, suggesting altered cell adhesion and migration pathways.

Keywords:
NIFTPsfollicular-patterned thyroid lesionsmiRNAsthyroid

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were reclassified from encapsulated follicular variants of papillary thyroid carcinomas.
  • NIFTPs behave similarly to follicular adenomas, distinct from invasive follicular variants of papillary thyroid carcinomas (FVPTCs).
  • MicroRNAs (miRNAs) are implicated in carcinogenesis and show potential as diagnostic/prognostic markers for thyroid cancer.

Purpose of the Study:

  • To investigate miRNA expression profiles in wild-type and mutated NIFTPs, FVPTCs, and follicular adenomas.
  • To identify molecular pathways associated with deregulated miRNAs in different thyroid tumor subtypes.
  • To assess the utility of miRNA expression combined with mutational status for improving thyroid cancer diagnosis.

Main Methods:

  • Utilized the nCounter miRNA Expression assay (NanoString Technologies) to analyze miRNA expression.
  • Compared miRNA profiles across wild-type NIFTPs, RAS/BRAF-mutated NIFTPs, infiltrative/invasive FVPTCs, and follicular adenomas.
  • Employed DNA Intelligent Analysis (DIANA) miRPath software to identify significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways linked to miRNA deregulation.

Main Results:

  • Distinct miRNA expression profiles were observed between wild-type and mutated NIFTPs.
  • Wild-type NIFTPs exhibited miRNA profiles similar to follicular adenomas.
  • Mutated NIFTPs displayed miRNA profiles resembling infiltrative and invasive FVPTCs, with specific miRNA up/downregulations linked to cell adhesion and migration pathways.

Conclusions:

  • MiRNA expression profiles can distinguish NIFTPs based on the presence or absence of RAS/BRAF mutations.
  • Mutated NIFTPs may possess an invasive-like phenotype, indicated by miRNA deregulation in key cellular pathways.
  • MiRNA analysis holds promise for enhancing the diagnostic accuracy of thyroid neoplasms.