Abstract 6095: SMOC2 as a potential biomarker with diagnostic value in uterine leiomyosarcoma

Abstract Uterine leiomyosarcoma (uLMS) is a rare and aggressive malignant tumor with poor prognosis. In contrast, uterine leiomyoma (uLM) is the most common benign tumor of the uterus found in women of reproductive age. Extracellular matrix (ECM) accumulation and remodeling are thought to be crucial for the development of these two tumors. To better understand the differences of ECM dynamics in these tumors, we have collected samples from 67 uLMS, 66 uLM and 68 normal myometrium (MM) which were analyzed by RNAseq (Illumina) and a high-resolution isoelectric focusing (HiRIEF) liquid chromatography-mass spectrometry (LC-MS)-based method (Dionex UltiMate™ 3000 RSLCnano System coupled to a Q-Exactive mass spectrometer, Thermo Scientific). After meta-analysis between uLM and uLMS groups using DESeq2 and edgeR, 112 genes were defined as common shared differentiatly expressed genes (DEG). Specific uLMS DEG were analyzed by gene ontology, KEGG pathway, and Reactome pathway. In the top 10 ranking of most affected biological processes/molecular functions/cellular components, we identified the gene SMOC2, a secreted calcium-binding protein of the BM-40/SPARC family which is present in the ECM and has been shown to be involved in fibrosis by modulating TGF-β1. SMOC2 is upregulated in uLM and is downregulated in both RNA and protein expression level in uLMS, compared to MM samples. We also observed that the TGFB1 pathway is downregulated in uLMS and upregulated in uLM, suggesting that this may induce high production of ECM which is related to fibrosis. In conclusion, this preliminary data shows SMOC2 as a potential biomarker to differentiate uLM and uLMS at the protein level and we plan to further study the role of SMOC2 in cell lines to improve our understanding on uLMS malignancy. Citation Format: Chen Cai, Raul Falcao, Georgia Kokaraki, Jorge Estefano Souza, Gustavo de Souza, Joseph Woodard Carlson, Tirzah Braz Petta. SMOC2 as a potential biomarker with diagnostic value in uterine leiomyosarcoma [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 6095.