{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:36:25Z","timestamp":1791999385096,"version":"4.4.0"},"reference-count":60,"publisher":"Bioscientifica","issue":"3","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":264,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Mutations of RAS genes are detected in a spectrum of follicular-patterned thyroid tumors. Preoperative prediction of invasive cancers based on the presence of RAS mutation alone is challenging because non-invasive and invasive tumors tend to have similar sonographic and cytologic features. The aim of this study was to perform clinicopathologic and molecular analyses of RAS-mutant tumors, identify molecular and clinical markers associated with invasiveness, and determine their diagnostic and therapeutic potentials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We collected clinicopathologic characteristics and performed RNA-seq on 48 surgically resected RAS-mutant thyroid tumors (23 non-invasive and 25 invasive). A classifier using expression data of selected invasiveness markers and clinical parameters was applied to an independent set of 54 RAS-mutant fine-needle aspiration (FNA) samples to predict invasion. Selected markers were investigated in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>On RNA-seq analysis, invasive RAS-mutant tumors showed different gene expression profiles compared to non-invasive tumors. Expression levels of six selected genes (CA12, CD44, LRP4, ECM1, FN1, and CRABP1) were associated with invasiveness on qRT-PCR. Expression levels of these genes plus nodule size predicted invasion in RAS-mutant FNA samples with 95% sensitivity and 89% specificity. siRNA silencing and chemical inhibition of CA12 reduced invasion of RAS-mutant human thyroid cells. Treatment of RAS-mutant xenografts with CA12 inhibitors arrested tumor growth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Development of invasion in RAS-mutant tumors is associated with significant alteration in gene expression. Expression levels of six genes and nodule size may predict invasion in RAS-mutant thyroid nodules, whereas chemical inhibition of CA12 may have a potential therapeutic effect in RAS-mutant tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/etj-25-0022","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T13:47:12Z","timestamp":1748526432000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-17","source":"Crossref","is-referenced-by-count":7,"title":["Alterations in gene expression associated with invasion of RAS-mutant thyroid tumors and their potential diagnostic and therapeutic utility"],"prefix":"10.1530","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4569-5398","authenticated-orcid":true,"given":"Vincenzo","family":"Condello","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Pittsburgh 1 , , ,","place":["Pittsburgh, Pennsylvania, 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