Abstract 776: Expression of SOX15 and Wnt pathway genes in papillary thyroid carcinoma

Abstract

Abstract Although thyroid cancer (TC) is a rare cancer with a rate of 2.1%, it is the most common cancer type among endocrine tumors. The molecular mechanisms of thyroid cancer, which develops as a result of environmental and genetic factors, are still unclear. SOX family genes are transcription factors that are expressed in a tissue-specific manner and play a role in the developmental processes. SRY-box transcription factor 15 (SOX15) is an important member of the SOX family and is involved in carcinogenesis. Its downregulation has been associated with the development and progression of different human malignancies. Some SOX family members have been reported to control cell proliferation by acting as negative regulators of the Wnt/β-catenin signaling pathway. MYC, CCND1 and CTNNB1 genes are important components of the Wnt signaling pathway. Recently, we have shown that epigenetic silencing of the SOX15 gene is associated with the pathogenesis of papillary thyroid carcinoma,In the present study, to further the understanding of the molecular mechanisms of SOX15 in papillary thyroid carcinoma (PTC) we investigated SOX15 expression in association with the transcriptional targets of the Wnt/β-catenin pathway.Primary thyroid tumors and adjacent nonmalignant tissue samples were collected from 52 patients, prior to any treatment. Total RNA was isolated from tissue samples and reverse transcription was performed. Expression levels of the SOX15, CTNNB1, c-MYC and CCND1 genes were analyzed by qRT-PCR using the SYBR green and Light-Cycler 480 system (Roche Diagnostics, Germany). β2M was used as the reference to normalize the mRNA levels. Statistical analysis was performed using the SPSS 21.0 (IBM® SPSS® Statistics, IBM Corporation Somers, NY, USA) program.SOX15 gene expression was significantly downregulated in 64.6% of PTC tissues compared to their normal counterparts. In contrast, CCND1, CTNNB1 and c-MYC gene expressions were significantly upregulated in 70.2%, 60% and 57.8% of the patients. Among the group of patients with downregulated SOX15 expression CCND1, CTNNB1 and c-MYC expression were upregulated in 46.8%, 40% and 40% of the subjects, respectively. Our data suggest that SOX15 downregulation may contribute to activation of Wnt signaling and provides further evidence indicating involvement of SOX15 in modulating the Wnt/β-catenin pathway in thyroid carcinogenesis. Citation Format: Ayse Nur Buyru, Ayşegul Soysal, Ahmet Ozaydın, Betul Seyhan, Soykan Arıkan, Nejat Dalay. Expression of SOX15 and Wnt pathway genes in papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 776.