Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor

Abstract

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.

Unraveling the Immune Microenvironment of Thymic Epithelial Tumors: Implications for Autoimmunity and Treatment

“…On the other hand, there is no notable difference in the concentration of CD68+ macrophages among thymoma subtypes and TCs. Despite their distribution variations among different TET categories, both TAM populations (CD68+ and CD 163+) are associated with tumor invasion and nodular metastases [ 26 , 30 ].…”

Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment

“…All samples were obtained with informed consent, and the study was approved by the Ethics Committee of Anhui Medical University, as well as the principles expressed in the Declaration of Helsinki. Immunohistochemistry was performed on formalin-xed, para n-embedded human tissue sections using a biotin-avidin method as described before [12]. Sections were developed with DAB and counterstained with hematoxylin.…”

CENPE is a potentially key molecular biomarker and potential therapeutic target for lung adenocarcinoma

“…Immunohistochemistry was performed as described before [23]|. Sections were developed with DAB and counterstained with hematoxylin.…”

“…Whole-slide imaging was taken using PANNORAMIC 1000 (3D-HISTECH, Hungary). Quantification of CENPE, CD11b and CD33 IHC chromogen intensity was performed as previously described [23]. The IHC scores of the staining proteins were evaluated by a pathologist.…”