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Czarnecka-Chrebelska 1, *  \nCitation: Soboska, K.; Kusi ´nski, M.; Pawelczyk, K.; Migdalska-S˛ek, M.; Brzezia ´nska-Lasota, E.; CzarneckaChrebelska, K.H. Expression of RASSF1A, DIRAS3, andAKAP9 Genes in Thyroid Lesions: Implications for Differential Diagnosis and Prognosis of Thyroid Carcinomas. Int. J. Mol. Sci. 2024, 25, 562. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms25010562](10.3390/ijms25010562)  \nAcademic Editor: Vija Lavinia  \nReceived: 21 November 2023  \nRevised: 25 December 2023  \nAccepted: 27 December 2023  \nPublished: 1 January 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Biomedicine and Genetics, Medical University of Lodz, 251 Str. Pomorska, 92-213 Lodz, Poland; [monika.migdalska-sek@umed.lodz.pl](monika.migdalska-sek@umed.lodz.pl) (M.M.-S.)  \n2 Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; [kamila.soboska@biol.uni.lodz.pl](kamila.soboska@biol.uni.lodz.pl)  \n3 Department of Endocrine, General and Vascular Surgery, Medical University of Lodz, 62 Str. Pabianicka, 93-513 Lodz, Poland; [michal.kusinski@umed.lodz.pl](michal.kusinski@umed.lodz.pl)  \n4 Faculty of Medicine, Medical University of Lodz, Av. Ko´sciuszki 4, 90-419 Lodz, Poland  \n* Correspondence: [karolina.czarnecka@umed.lodz.pl](karolina.czarnecka@umed.lodz.pl)  \nAbstract: Thyroid carcinoma is the primary endocrine malignancy worldwide. The preoperative examination of thyroid tissue lesion is often unclear. Approximately 25% of thyroid cancers cannot be diagnosed definitively without post-surgery histopathological examination. The assessment of diagnostic and differential markers of thyroid cancers is needed to improve preoperative diagnosis and reduce unnecessary treatments. Here, we assessed the expression of RASSF1A, DIRAS3, and AKAP9 genes, and the presence of BRAF V600E point mutation in benign and malignant thyroid lesions in a Polish cohort (120 patients) . We have also performed a comparative analysis of gene expression using data obtained from the Gene Expression Omnibus (GEO) database (307 samples) . The expression of RASSF1A and DIRAS3 was decreased, whereas AKAP9’s was increased in pathologically changed thyroid compared with normal thyroid tissue, and significantly correlated withe.g., histopathological type of lesion papillary thyroid cancer (PTC) vs follicular thyroid cancer (FTC), patient’s age, tumour stage, or its encapsulation. The receiver operating characteristic (ROC) analysis for the more aggressive FTC subtype differential marker suggests value in estimating RASSF1A and AKAP9 expression, with their area under curve (AUC), specificity, and sensitivity at 0.743 (95% CI: 0.548–0.938), 82.2%, and 66.7%; for RASSF1A, and 0.848 (95% CI: 0.698–0.998), 54.8%, and 100%, for AKAP9 . Our research gives new insight into the basis of the aggressiveness and progression of thyroid cancers, and provides information on potential differential markers that may improve preoperative diagnosis.  \nKeywords: thyroid carcinoma; thyroid nodules; signalling pathways; BRAF V600E; RASSF1A; DIRAS3; AKAP9  \n1. Introduction  \nThyroid carcinoma is the ninth most frequently detected cancer disease and the primary endocrine malignancy worldwide, with the most often recognised histological types (95%) derived from thyroid follicu","cbCairTFPePFu3Ge","https://ap.wps.com/l/cbCairTFPePFu3Ge","pdf",1965769,21,"English","# Abstract\n# 1. Introduction","[{\"question\":\"Why is preoperative diagnosis of thyroid lesions often unclear?\",\"answer\":\"Preoperative examination of thyroid tissue lesions, including fine-needle aspiration biopsy, is often inconclusive. In a substantial fraction of cases, definitive diagnosis requires postoperative histopathological evaluation.\"},{\"question\":\"Which genes and mutation were assessed in the study?\",\"answer\":\"The study assessed expression of RASSF1A, DIRAS3, and AKAP9 genes and evaluated the presence of the BRAF V600E point mutation in benign and malignant thyroid lesions.\"},{\"question\":\"What expression trends were observed between normal and pathologically changed thyroid tissue?\",\"answer\":\"RASSF1A and DIRAS3 expression decreased, while AKAP9 expression increased in pathologically changed thyroid compared with normal thyroid tissue.\"}]","Expression of RASSF1A, DIRAS3, and AKAP9 Genes in Thyroid Lesions - Implications for Differential Diagnosis and Prognosis of Thyroid Carcinomas | PDF",1789975067,53]