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 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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Numb modulates intestinal epithelial cells toward goblet cell phenotype by inhibiting the Notch signaling pathway

Experimental Cell Research ◽

10.1016/j.yexcr.2011.04.008 ◽

2011 ◽

Vol 317 (11) ◽

pp. 1640-1648 ◽

Cited By ~ 16

Author(s):

Yongtao Yang ◽

Rong Zhu ◽

Jianying Bai ◽

Xin Zhang ◽

Yin Tian ◽

...

Keyword(s):

Epithelial Cells ◽

Notch Signaling ◽

Signaling Pathway ◽

Goblet Cell ◽

Intestinal Epithelial Cells ◽

Notch Signaling Pathway ◽

Cell Phenotype ◽

Intestinal Epithelial

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Analysis of transcriptomic changes in bovine endometrial stromal cells treated with lipopolysaccharide

10.21203/rs.2.16904/v2 ◽

2020 ◽

Author(s):

Xuefen Ding ◽

Haimiao Lv ◽

Lixin Deng ◽

Wenju Hu ◽

Zhan Peng ◽

...

Keyword(s):

Epithelial Cells ◽

Signaling Pathway ◽

Stromal Cells ◽

Interleukin 12 ◽

Receptor Interaction ◽

Control Group ◽

Receptor Signaling ◽

Toll Like Receptor ◽

Endometrial Stromal Cells ◽

Receptor Signaling Pathway

Abstract Background: Endometritis adversely affects the ability of cattle to reproduce, and significantly reduces milk production. Consequently, it has great influence on the economic value of dairy cows. The endometrium is mainly composed of epithelial and stromal cells and they produce the first immune response to invading pathogens. Epithelial cells are the first cellular barrier through which bacteria enter the uterine endometrium. However, most of the epithelial cells are disrupted and stromal cells are exposed to an inflammatory environment when endometritis occurs, especially postpartum. A loss of the protective epithelium allows bacteria or toxins to access the underlying stromal cells. The activation of Toll-like receptor（TLRs）on stromal cells induces increased production of cytokines and chemokines. Understanding the genome-wide characterization of the bovine endometritis will be beneficial for prevention and treatment of endometritis. In this study, whole-transcriptomic gene changes in bovine stromal cells treated with LPS were compared with those treated with PBS (control group) and were analyzed by RNA sequencing (RNA-seq). Results: Compared with the control group, a total of 366 differentially expressed genes (DEGs) were identified in LPS-induced group (234 upregulated and 132 downregulated genes), with an adjusted P-value＜0.05 by DESeq. Gene ontology (GO) enrichment analysis revealed DEGs were most enriched in lymphocyte activation, interleukin-1 receptor binding, regulation of cell activation, and lymphocyte-activated interleukin-12 production. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed DEGs were most enriched in TNF signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, nucleotide-binding oligomerization domain-like (NOD-like) receptor signaling pathway, NF-κB signaling pathway, and chemokine signaling pathway.Conclusion: The results of this study unraveled endometrial stromal cells transcriptome profile alterations in bovine affected by LPS which may have a significant effect on the eliminating or reducing inflammation by comprehending molecular mechanisms and authenticating unique genes related to endometritis.

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Analysis of transcriptomic changes in bovine endometrial stromal cells treated with lipopolysaccharide

10.21203/rs.2.16904/v3 ◽

2020 ◽

Author(s):

Xuefen Ding ◽

Haimiao Lv ◽

Lixin Deng ◽

Wenju Hu ◽

Zhan Peng ◽

...

Keyword(s):

Epithelial Cells ◽

Signaling Pathway ◽

Stromal Cells ◽

Interleukin 12 ◽

Receptor Interaction ◽

Control Group ◽

Receptor Signaling ◽

Toll Like Receptor ◽

Endometrial Stromal Cells ◽

Receptor Signaling Pathway

Abstract Background: Endometritis adversely affects the ability of cattle to reproduce, and significantly reduces milk production. Consequently, it has great influence on the economic value of dairy cows. The endometrium is mainly composed of epithelial and stromal cells and they produce the first immune response to invading pathogens. Epithelial cells are the first cellular barrier through which bacteria enter the uterine endometrium. However, most of the epithelial cells are disrupted and stromal cells are exposed to an inflammatory environment when endometritis occurs, especially postpartum. A loss of the protective epithelium allows bacteria or toxins to access the underlying stromal cells. The activation of Toll-like receptor（TLRs）on stromal cells induces increased production of cytokines. Understanding the genome-wide characterization of the bovine endometritis will be beneficial for prevention and treatment of endometritis. In this study, whole-transcriptomic gene changes in bovine stromal cells treated with LPS were compared with those treated with PBS (control group) and were analyzed by RNA sequencing (RNA-seq). This was done in a cell culture model in vitro.Results: Compared with the control group, a total of 366 differentially expressed genes (DEGs) were identified in LPS-induced group (234 upregulated and 132 downregulated genes), with an adjusted P-value＜0.05 by DESeq. Gene ontology (GO) enrichment analysis revealed DEGs were most enriched in lymphocyte activation, interleukin-1 receptor binding, regulation of cell activation, and lymphocyte-activated interleukin-12 production. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed DEGs were most enriched in TNF signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, nucleotide-binding oligomerization domain-like (NOD-like) receptor signaling pathway, NF-κB signaling pathway, and chemokine signaling pathway.Conclusion: The results of this study unraveled bovine endometrial stromal cells affected with LPS transcriptome profile alterations，which may have a significant effect on the treatment inflammation by comprehending molecular mechanisms and authenticating unique genes related to endometritis.

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CD74 regulates cellularity and maturation of medullary thymic epithelial cells partially by activating the canonical NF‐κB signaling pathway

The FASEB Journal ◽

10.1096/fj.202100139r ◽

2021 ◽

Vol 35 (5) ◽

Author(s):

Hong‐Xia Wang ◽

Qian Zhang ◽

Jiayu Zhang ◽

Rong Luan ◽

Zhanfeng Liang ◽

...

Keyword(s):

Epithelial Cells ◽

Signaling Pathway ◽

Thymic Epithelial Cells ◽

Medullary Thymic Epithelial Cells

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Identification of Core Biomarkers Associated with Outcome in Glioma: Evidence from Bioinformatics Analysis

Disease Markers ◽

10.1155/2018/3215958 ◽

2018 ◽

Vol 2018 ◽

pp. 1-16 ◽

Cited By ~ 3

Author(s):

Rong-Xin Geng ◽

Ning Li ◽

Yang Xu ◽

Jun-hui Liu ◽

Fan-en Yuan ◽

...

Keyword(s):

Signaling Pathway ◽

Bioinformatics Analysis ◽

Receptor Interaction ◽

Normal Brain ◽

Gabaergic Synapse ◽

Protein Protein Interaction ◽

P53 Signaling ◽

Kaplan Meier ◽

Search Tool ◽

Upregulated Genes

Glioma is the most common neoplasm of the central nervous system (CNS); the progression and outcomes of which are affected by a complicated network of genes and pathways. We chose a gene expression profile of GSE66354 from GEO database to search core biomarkers during the occurrence and development of glioma. A total of 149 samples, involving 136 glioma and 13 normal brain tissues, were enrolled in this article. 1980 differentially expressed genes (DEGs) including 697 upregulated genes and 1283 downregulated genes between glioma patients and healthy individuals were selected using GeoDiver and GEO2R tool. Then, gene ontology (GO) analysis as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) plug-in was employed to imagine protein-protein interaction (PPI) of these DEGs. The upregulated genes were enriched in cell cycle, ECM-receptor interaction, and p53 signaling pathway, while the downregulated genes were enriched in retrograde endocannabinoid signaling, glutamatergic synapse, morphine addiction, GABAergic synapse, and calcium signaling pathway. Subsequently, 4 typical modules were discovered by the PPI network utilizing MCODE software. Besides, 15 hub genes were chosen according to the degree of connectivity, including TP53, CDK1, CCNB1, and CCNB2, the Kaplan-Meier analysis of which was further identified. In conclusion, this bioinformatics analysis indicated that DEGs and core genes, such as TP53, might influence the development of glioma, especially in tumor proliferation, which were expected to be promising biomarkers for diagnosis and treatment of glioma.

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Identification of Potential Hub Genes and Therapeutic Drugs in Malignant Pleural Mesothelioma by Integrated Bioinformatics Analysis

Oncology Research and Treatment ◽

10.1159/000510534 ◽

2020 ◽

Vol 43 (12) ◽

pp. 656-671

Author(s):

Xiangxin Zhang ◽

Liu Yang ◽

Wei Chen ◽

Ming Kong

Keyword(s):

Gene Expression ◽

Signaling Pathway ◽

Malignant Pleural Mesothelioma ◽

Poor Prognosis ◽

Bioinformatics Analysis ◽

Asbestos Exposure ◽

Receptor Interaction ◽

Pleural Mesothelioma ◽

Hub Genes ◽

The Impact

Introduction: Malignant pleural mesothelioma (MPM) is closely linked to asbestos exposure and is an extremely aggressive tumor with poor prognosis. Objective: Our study aimed to elucidate hub genes and potential drugs in MPM by integrated bioinformatics analysis. Methods: GSE42977 was download from the Gene Expression Omnibus (GEO) database; the differentially expressed genes (DEGs) with adj.p value <0.05 and |logFC| ≥2 were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by DAVID database. The STRING database was used to construct a protein-protein interaction network, and modules analysis and hub genes acquisition were performed by Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to assess the impact of hub genes on the prognosis of MPM patients. The Drug-Gene Interaction database (DGIdb) was used to select the related drugs. Results: A total of 169 upregulated and 70 downregulated DEGs were identified. These DEGs are enriched in the pathway of extracellular matrix-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and PPAR signaling pathway. Finally, 10 hub genes (CDC20, CDK1, UBE2C, TOP2A, CCNB2, NUSAP1, KIF20A, AURKA, CEP55, and ASPM) were identified, which are considered to be closely related to the poor prognosis of MPM. In addition, 119 related drugs that may have a therapeutic effect on MPM were filtered out. Conclusion: These discovered genes and small-molecule drugs provide some new ideas for further research on MPM.

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Analysis of transcriptomic changes in bovine endometrial stromal cells treated with lipopolysaccharide

10.21203/rs.2.16904/v1 ◽

2019 ◽

Author(s):

Xuefen Ding ◽

Haimiao Lv ◽

Lixin Deng ◽

Wenju Hu ◽

Zhan Peng ◽

...

Keyword(s):

Epithelial Cells ◽

Signaling Pathway ◽

Stromal Cells ◽

Molecular Mechanisms ◽

Interleukin 12 ◽

Receptor Interaction ◽

Control Group ◽

Receptor Signaling ◽

Endometrial Stromal Cells ◽

Receptor Signaling Pathway

Abstract Background: Endometritis adversely affects the ability of cattle to reproduce, and significantly reduces milk production. Consequently, it has great influence on the economic value of dairy cows. The endometrium is mainly composed of epithelial and stromal cells and they produce the first immune response to invading pathogens. Epithelial cells are the first cellular barrier through which bacteria enter the uterine endometrium. However, most of the epithelial cells are disrupted and stromal cells are exposed to an inflammatory environment when endometritis occurs, especially postpartum. Inflammation in endometrial stromal cells is thus activated, immune-related cytokines and signaling pathways are activated. This indicates that endometritis is becoming more and more serious. However, inflammatory response in bovine endometrial stromal cells is yet to be studied in detail. Understanding the genome-wide characterization of the bovine endometritis will be beneficial for prevention and treatment of endometritis. In this study, whole-transcriptomic gene changes in bovine stromal cells treated with LPS were compared with those treated with PBS (control group) and were analyzed by RNA sequencing (RNA-seq). Results: Compared with the control group, a total of 366 differentially expressed genes (DEGs) were identified in LPS-induced group (234 upregulated and 132 downregulated genes), with an adjusted P -value＜0.05 by DESeq. Gene ontology (GO) enrichment analysis revealed DEGs were most enriched in lymphocyte activation, interleukin-1 receptor binding, regulation of cell activation, and lymphocyte-activated interleukin-12 production. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed DEGs were most enriched in TNF signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, nucleotide-binding oligomerization domain-like (NOD-like) receptor signaling pathway, NF-κB signaling pathway, and chemokine signaling pathway. Conclusion: Our results proved and expanded findings of previous studies on bovine endometritis. These results will be useful to propose new therapeutic targets and eliminate or reduce inflammation by comprehending molecular mechanisms and authenticating unique genes related to endometritis.

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Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas

10.1101/317297 ◽

2018 ◽

Author(s):

Jean-Michel Maury ◽

Claire Merveilleux du Vignaux ◽

Gabrielle Drevet ◽

Virginie Zarza ◽

Lara Chalabreysse ◽

...

Keyword(s):

Cell Proliferation ◽

Epithelial Cells ◽

Cell System ◽

Mtor Pathway ◽

Thymic Epithelial Cells ◽

Thymic Epithelial Tumors ◽

Molecular Abnormalities ◽

Short Period ◽

Thymic Tumors

AbstractThe pathogenesis of thymic epithelial tumors remains poorly elucidated. The PI3K/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II study reported a positive effect of mTOR inhibitors in disease control in thymoma patients. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell systemWe analyzed protein expression and activation of key players of the Akt/mTOR pathway namely Akt, mTOR, and P70S6K in thirteen A, B and AB thymomas as well as in normal thymuses. While only Akt and the phospho-Akt were expressed in normal thymuses, both Akt and mTOR were activated, with B2 thymomas expressing higher level of activated phospho-Akt than A or AB subtypes. Phospho-P70S6K was expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. Interestingly, in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas, we report the activation of Akt; mTOR and P70S6. Finally, we analyzed the effect of mTOR inhibitor on thymoma derived epithelial cells and showed that rapamycin (100 nM/ ml) significantly reduced cell proliferation.Our results suggest that the activation of the Akt/ mTOR pathway might participate to the cell proliferation associated with tumor growth. Ultimately, our data enhance the potential role of thymic epithelial cells derived from tissue specimens forin vitroexploration of molecular abnormalities specific to rare thymic tumors.

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Altered thymic epithelial cells may be decisive for Moloney virus-induced lymphoma development

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077499 ◽

1983 ◽

Vol 41 ◽

pp. 784-785

Author(s):

U.I. Heine ◽

G.R.F. Krueger ◽

E. Munoz ◽

A. Karpinski

Keyword(s):

Epithelial Cells ◽

Leukemia Virus ◽

Light And Electron Microscopy ◽

Tumor Development ◽

Current Evidence ◽

Thymic Epithelial Cells ◽

Thymic Tissue ◽

Newborn Mice ◽

Moloney Leukemia Virus ◽

Differentiation Block

Infection of newborn mice with Moloney leukemia virus (M-MuLV) causes a T-cell differentiation block in the thymic cortex accompanied by proliferation and accumulation of prethymic lymphoblasts in the thymus and subsequent spreading of these cells to generate systemic lymphoma. Current evidence shows that thymic reticular epithelial cells (REC) provide a microenvironment necessary for the maturation of prethymic lymphoblasts to mature T-lymphocytes by secretion of various thymic factors. A change in that environment due to infection of REC by virus could be decisive for the failure of lymphoblasts to mature and thus contribute to lymphoma development.We have studied the morphology and distribution of the major thymic cell populations at different stages of tumorigenesis in Balb/c mice infected when newborn with 0.2ml M-MuLV suspension, 6.8 log FFU/ml. Thymic tissue taken at 1-2 weekly intervals up to tumor development was processed for light and electron microscopy, using glutaraldehyde-OsO4fixation and Epon-Araldite embedding.

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