Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor.
Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor.
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DOI：
10.3389/fonc.2021.708735
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发表时间：
2021
影响因子：
4.7
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Yuan X;Huang L;Luo W;Zhao Y;Nashan B;Yu F;Liu Y
胸腺上皮肿瘤(TETS)是一种罕见的起源于胸腺上皮细胞的肿瘤。SOX9是SOX(SRY相关高迁移率族盒)基因家族的一员，被认为是多种癌症的癌基因和治疗靶点。然而，它在Tets中的角色仍然不确定。应用免疫组织化学方法检测34例胸腺瘤(A型8例，AB型6例，B1型6例，B2型9例，B3型5例)和20例胸腺癌组织中SOX9的表达，并探讨其临床病理和预后意义。进一步对SOX9高表达和低表达的胸腺瘤的基因表达谱进行生物信息学分析，并根据癌症基因组图谱(TCGA)数据库中确定的胸腺瘤病例进行相应的生存分析，以SOX9的中位数表达水平为界值。免疫组织化学染色显示，SOX9在Hassall小体上皮细胞和Tet肿瘤细胞胞核中高表达。SOX9的表达与胸腺瘤的组织学类型显著相关，高表达提示胸腺瘤的临床预后不良。生物信息学分析表明，与SOX9表达正相关的基因定位于肿瘤的蛋白多糖、细胞黏附分子、参与细胞外基质-受体相互作用的分子和转化生长因子-β信号通路，与SOX9表达负相关的基因定位于原发免疫缺陷、T细胞受体信号通路、Th17细胞分化、PD-L1表达和PD-1检查点通路。此外，SOX9的表达与丛状细胞的主要调控因子POU2F3和Trpm5的表达呈正相关，提示SOX9的高表达可能与胸腺瘤的丛状细胞表型有关。此外，SOX9的高表达与胸腺瘤的免疫调节失调有关，在SOX9高表达组中M2巨噬细胞明显占优势。SOX9可作为TETS的诊断和预后指标。值得注意的是，TETS中SOX9的高表达可能表明胸腺瘤的簇状细胞表型和免疫抑制微环境。
Thymic 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. Using 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. Immunohistochemistry 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. SOX9 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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DOI：
10.1073/pnas.1720948115
发表时间：
2018-04-24
影响因子：
11.1
作者：
Peranzoni E;Lemoine J;Vimeux L;Feuillet V;Barrin S;Kantari-Mimoun C;Bercovici N;Guérin M;Biton J;Ouakrim H;Régnier F;Lupo A;Alifano M;Damotte D;Donnadieu E
通讯作者：
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影响因子：
5.8
作者：
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影响因子：
4.4
作者：
Rattay, Kristin;Claude, Janine;Derbinski, Jens
通讯作者：
Derbinski, Jens
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影响因子：
28.5
作者：
Ma, Xiao-Lu;Hu, Bo;Lu, Ren-Quan
通讯作者：
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影响因子：
11.5
作者：
Jiang, Shih Sheng;Fang, Wen-Tsen;Chang, I-Shou
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