{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T15:02:32Z","timestamp":1763650952450,"version":"3.45.0"},"reference-count":78,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, yet the transcriptional hierarchies linking endocrine signaling to tumor progression remain poorly defined. Here, we integrated gene-expression profiles from two independent cohorts (TCGA-THCA and GSE33630) to identify consensus transcriptional master regulators (TMRs) driving PTC. After normalization and differential expression analysis, we reconstructed regulon networks with ARACNe-AP, inferred TMR activity using VIPER, and integrated evidence across datasets via Fisher\u2019s meta-analysis. This cross-cohort strategy yielded 50 shared TMRs, predominantly from the Zinc Finger, Forkhead, ETS, and nuclear receptor families. Network topology highlighted PBX4, GATAD2A, BHLHE40, HEY2, and TEAD4 as upstream regulators controlling other TMRs. Functional enrichment revealed activation of NOTCH, MAPK, PI3K, and TGF-\u03b2 signaling and enrichment of early and late estrogen-response programs, uncovering a noncanonical role of SMAD9 in TGF-\u03b2 signaling. Together, these findings delineate the transcriptional and hormonal circuitry underlying thyroid tumorigenesis, providing a regulatory framework for biomarker-driven therapies based on network activity states.<\/jats:p>","DOI":"10.3390\/ijms262211231","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T15:00:17Z","timestamp":1763650817000},"page":"11231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Two Cohorts, One Network: Consensus Master Regulators Orchestrating Papillary Thyroid Carcinoma"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0979-2203","authenticated-orcid":false,"given":"Diana","family":"Tapia-Carrillo","sequence":"first","affiliation":[{"name":"Escuela Nacional Preparatoria Plantel 9 \u201cPedro de Alba\u201d, Universidad Nacional Aut\u00f3noma de Mexico, Mexico City 07300, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-6637","authenticated-orcid":false,"given":"Octavio","family":"Zambada-Moreno","sequence":"additional","affiliation":[{"name":"Deparment of Genetic Engineering, Center for Research and Advanced Studies (Cinvestav), Irapuato 36821, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-1397","authenticated-orcid":false,"given":"Enrique","family":"Hern\u00e1ndez-Lemus","sequence":"additional","affiliation":[{"name":"Computational Genomics Division, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-6133","authenticated-orcid":false,"given":"Hugo","family":"Tovar","sequence":"additional","affiliation":[{"name":"Computational Genomics Division, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"965212","DOI":"10.1155\/2013\/965212","article-title":"Worldwide Increasing Incidence of Thyroid Cancer: Update on Epidemiology and Risk Factors","volume":"2013","author":"Pellegriti","year":"2013","journal-title":"J. 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