Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor
BackgroundThymic epithelial tumors (TETs) are rare tumors originating from the thymic epithelial cells. SOX9, a member of the family of SOX (SRY-related high-mobility group box) genes, has been considered as an oncogene and therapeutic target in various cancers. However, its role in TETs remains unc...
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.708735/full |
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| author | Xiaodong Yuan Lei Huang Wenwu Luo Yufei Zhao Björn Nashan Fazhi Yu Yun Liu |
| author_facet | Xiaodong Yuan Lei Huang Wenwu Luo Yufei Zhao Björn Nashan Fazhi Yu Yun Liu |
| author_sort | Xiaodong Yuan |
| collection | DOAJ |
| description | BackgroundThymic epithelial tumors (TETs) are rare tumors originating from the thymic epithelial cells. SOX9, a member of the family of SOX (SRY-related high-mobility group box) genes, has been considered as an oncogene and therapeutic target in various cancers. However, its role in TETs remains uncertain.MethodsUsing the immunohistochemistry method, the expression of SOX9 was analyzed in TETs tissues, including 34 thymoma (8 cases with type A, 6 with type AB, 6 with type B1, 9 with type B2, and 5 with type B3 thymomas) and 20 thymic cancer tissues and the clinicopathologic and prognostic significances were evaluated. Further bioinformatics analysis of gene expression profiles of thymomas with high and low SOX9 expressions and the corresponding survival analyses were based on the thymoma cases identified in The Cancer Genome Atlas (TCGA) database, with the median expression level of SOX9 selected as cutoff.ResultsImmunohistochemistry staining showed that SOX9 was highly expressed in the nuclei of the epithelial cells of the Hassall’s corpuscles and of the TET tumor cells. SOX9 expression was significantly associated with histological type and high expression indicated unfavorable clinical outcomes of thymomas. Bioinformatics analysis revealed that genes positively associated with SOX9 expression were mapped in proteoglycans in cancer, cell adhesion molecules, and molecules involved in extracellular matrix-receptor interaction and the TGF-β signaling pathway, and that genes negatively associated with SOX9 expression were mapped in molecules involved in primary immunodeficiency, the T cell receptor signaling pathway, Th17 cell differentiation, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. In addition, SOX9 expression was positively associated with POU2F3 and TRPM5 expressions, the master regulators of tuft cells, suggesting that high SOX9 expression might be associated with the tuft cell phenotype of thymomas. Moreover, high SOX9 expression was associated with immune dysregulation of thymoma, and M2 macrophage significantly dominated in the high SOX9 expression group.ConclusionSOX9 may serve as a diagnostic and prognostic marker for TETs. Notably, high SOX9 expression in TETs may indicate a tuft cell phenotype and an immune suppressive microenvironment of thymomas. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-17T23:23:38Z |
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| series | Frontiers in Oncology |
| spelling | doaj.art-a613afbd31574414ad1d4e12979f4ad62022-12-21T21:28:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-10-011110.3389/fonc.2021.708735708735Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial TumorXiaodong Yuan0Lei Huang1Wenwu Luo2Yufei Zhao3Björn Nashan4Fazhi Yu5Yun Liu6Organ Transplant Center, Department of Hepatobiliary and Transplantation Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Anhui Medical University, Hefei, ChinaDepartment of Radiation Oncology, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaOrgan Transplant Center, Department of Hepatobiliary and Transplantation Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaThe First Affiliated Hospital of USTC, School of Life Sciences, University of Science and Technology of China, Hefei, ChinaDepartment of Radiation Oncology, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaBackgroundThymic epithelial tumors (TETs) are rare tumors originating from the thymic epithelial cells. SOX9, a member of the family of SOX (SRY-related high-mobility group box) genes, has been considered as an oncogene and therapeutic target in various cancers. However, its role in TETs remains uncertain.MethodsUsing the immunohistochemistry method, the expression of SOX9 was analyzed in TETs tissues, including 34 thymoma (8 cases with type A, 6 with type AB, 6 with type B1, 9 with type B2, and 5 with type B3 thymomas) and 20 thymic cancer tissues and the clinicopathologic and prognostic significances were evaluated. Further bioinformatics analysis of gene expression profiles of thymomas with high and low SOX9 expressions and the corresponding survival analyses were based on the thymoma cases identified in The Cancer Genome Atlas (TCGA) database, with the median expression level of SOX9 selected as cutoff.ResultsImmunohistochemistry staining showed that SOX9 was highly expressed in the nuclei of the epithelial cells of the Hassall’s corpuscles and of the TET tumor cells. SOX9 expression was significantly associated with histological type and high expression indicated unfavorable clinical outcomes of thymomas. Bioinformatics analysis revealed that genes positively associated with SOX9 expression were mapped in proteoglycans in cancer, cell adhesion molecules, and molecules involved in extracellular matrix-receptor interaction and the TGF-β signaling pathway, and that genes negatively associated with SOX9 expression were mapped in molecules involved in primary immunodeficiency, the T cell receptor signaling pathway, Th17 cell differentiation, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. In addition, SOX9 expression was positively associated with POU2F3 and TRPM5 expressions, the master regulators of tuft cells, suggesting that high SOX9 expression might be associated with the tuft cell phenotype of thymomas. Moreover, high SOX9 expression was associated with immune dysregulation of thymoma, and M2 macrophage significantly dominated in the high SOX9 expression group.ConclusionSOX9 may serve as a diagnostic and prognostic marker for TETs. Notably, high SOX9 expression in TETs may indicate a tuft cell phenotype and an immune suppressive microenvironment of thymomas.https://www.frontiersin.org/articles/10.3389/fonc.2021.708735/fullSOX9POU2F3tuft cellthymic epithelial tumortumor microenvironment |
| spellingShingle | Xiaodong Yuan Lei Huang Wenwu Luo Yufei Zhao Björn Nashan Fazhi Yu Yun Liu Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor Frontiers in Oncology SOX9 POU2F3 tuft cell thymic epithelial tumor tumor microenvironment |
| title | Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor |
| title_full | Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor |
| title_fullStr | Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor |
| title_full_unstemmed | Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor |
| title_short | Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor |
| title_sort | diagnostic and prognostic significances of sox9 in thymic epithelial tumor |
| topic | SOX9 POU2F3 tuft cell thymic epithelial tumor tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.708735/full |
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