scholarly journals Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

2020 ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Kenneth S. Knox ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Immunological Response ◽  
Functional Enrichment ◽  
Genomic Biomarkers ◽  
Diagnosis And Prognosis ◽  
Genomic Markers ◽  
Affected Tissue ◽  
Granulomatous Diseases

Abstract Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods: Transcriptomic profiles of immune-related gene from micro-dissected lungs and mediastinal lymph nodes sarcoidosis granulomas was compared to infectious granulomas. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers, excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, CXCL2, FABP4 . Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. Conclusion : These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in two commonly affected tissue in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

scholarly journals Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

2020 ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Kenneth S. Knox ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Immunological Response ◽  
Functional Enrichment ◽  
Genomic Biomarkers ◽  
Diagnosis And Prognosis ◽  
Genomic Markers ◽  
Affected Tissue ◽  
Granulomatous Diseases

Abstract Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures.Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods: Transcriptomic profiles of immune-related gene from micro-dissected lungs and mediastinal lymph nodes sarcoidosis granulomas was compared to infectious granulomas. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers, excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, CXCL2, FABP4. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level.Conclusion: These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in two commonly affected tissue in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

scholarly journals Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L. Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Xiaoguang Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Mediastinal Lymph Node ◽  
Immunological Response ◽  
Functional Enrichment ◽  
Genomic Biomarkers ◽  
Genomic Markers ◽  
Embedded Blocks ◽  
Granulomatous Diseases

Abstract Rationale Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. Conclusion These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

scholarly journals Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

2020 ◽  
Author(s):  
Nancy G. Casanova ◽  
Manuel L Gonzalez-Garay ◽  
Belinda Sun ◽  
Christian Bime ◽  
Kenneth S. Knox ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Mediastinal Lymph Node ◽  
Immunological Response ◽  
Functional Enrichment ◽  
Genomic Biomarkers ◽  
Genomic Markers ◽  
Embedded Blocks ◽  
Granulomatous Diseases

Abstract Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures.Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis).Methods: Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways.Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level.Conclusion: These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

scholarly journals Sodium-iodide symporter (NIS) gene expression in lymph-node metastases of papillary thyroid carcinomas

2000 ◽  
pp. 623-627 ◽  
Author(s):  
F Arturi ◽  
D Russo ◽  
D Giuffrida ◽  
M Schlumberger ◽  
S Filetti
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Papillary Thyroid ◽  
Iodide Uptake ◽  
Metastatic Lymph Nodes ◽  
Thyroid Carcinomas ◽  
Metastatic Lymph ◽  
Nis Gene ◽  
Total Body

OBJECTIVE: To investigate the molecular mechanisms underlying the influence of alteration of iodine trapping on the prognosis of metastatic papillary thyroid carcinomas, focusing on the expression of the Na+/I(-) symporter (NIS). DESIGN: We evaluated the expression of the NIS gene in a series of 11 enlarged neck lymph-node metastases of papillary thyroid carcinomas, including four patients in whom an enlarged lymph node represented the first sign of the tumoral disease. Nine lymph nodes, either reactive or metastatic for non-thyroid tumors, were also investigated. METHODS: Expression of the NIS gene was evaluated by RT-PCR in material obtained by fine-needle aspiration biopsy. RESULTS: The NIS gene was expressed in eight (73%) of 11 differentiated thyroid cancer metastatic lymph nodes examined. Five of these metastatic lymph nodes were positive at the post-treatment total-body iodine-131 scan; in the other three, the total-body scan showed no uptake in the metastatic tissues, indicating an alteration downstream to the NIS mRNA synthesis causing the loss of iodide uptake. As expected, when the NIS mRNA expression was absent, total-body (131)I scan showed no uptake in the metastatic lymph nodes. CONCLUSIONS: Our study demonstrates that NIS gene expression may be absent in metastatic differentiated thyroid carcinomas and that different mechanisms, other than loss of NIS transcription, may also be involved in the loss of iodide uptake in metastatic thyroid cells. Study of NIS gene expression in the metastatic lymph nodes, therefore, may provide useful information in the management of patients with thyroid carcinoma.

scholarly journals Siglec-15 Is an Immune Suppressor and Potential Target for Immunotherapy in the Pre-Metastatic Lymph Node of Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Hang Du ◽  
Jingling Tang ◽  
Xiaoyun Li ◽  
Xinjun Wang ◽  
Liyun Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Nodes ◽  
Metastatic Lymph Node ◽  
Sentinel Lymph Nodes ◽  
Node Metastasis ◽  
Metastatic Lymph ◽  
Colorectal Cancer Patients

Lymph node metastasis indicates a poor prognosis in colorectal cancer. To better understand the underlying mechanisms of lymph node metastasis, we analyzed transcriptome characteristics of the pre-metastatic lymph node, a putative microenvironment favorable for the seeding and proliferation of cancer cells. Thus, we tried to compare and elucidate the transcriptional and immune characteristics of sentinel lymph nodes (SNs) with matched non-sentinel lymph nodes (NSNs) in colorectal cancer patients. In this study, a total of 38 pairs of SNs and NSNs were collected, in which 26 pairs of non-metastatic lymph nodes were subjected to RNA-seq and bioinformatics analysis for the gene expression profiles. There were 16 differentially expressed genes between SNs and NSNs being identified, including 9 upregulated and 7 downregulated genes in SN. Gene Ontology (GO) classification analysis revealed that the differentially expressed genes were mainly involved in leukocyte differentiation, chemokine secretion, and immune system regulation. In the meantime, gene set enrichment analysis (GSEA) showed that immune-related signaling pathways, such as transforming growth factor beta (TGF-β) signaling and tumor necrosis factor alpha (TNF-α)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, were enriched in NSN, while cell proliferation–related signaling pathways were enriched in SN, including MYC signaling and G2M checkpoint signaling. We further identified SIGLEC15 as a top upregulated gene in SN. However, RNAscope assay showed that SIGLEC15 was not largely co-expressed with M2 macrophage marker CD163. We then selected eight pairs of lymph nodes for further cytological studies. Flow cytometry analysis revealed that Siglec-15 was expressed on all myeloid cell subsets. The relative expression of SEGLEC15 (SN/NSN) was correlated with the microsatellite instability (MSI) status in colorectal cancer patients. Further studies found that small interfering ribonucleic acid (siRNA)-mediated silencing of SLGLEC15 can enhance the anti-tumor function of T cells, as indicated by cytokine release analysis. In conclusion, we presented here a first report on the gene expression profiling of the pre-metastatic lymph node in colorectal cancer. The findings in this study suggest that SIGLEC15 plays an important role in SN immunosuppression. SEGLEC15 silencing could be a therapeutic strategy for restoring T cell function in tumor SNs.

scholarly journals Gene Expression Profiling of Lymph Node Sub-Capsular Sinus Macrophages in Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Danilo Pellin ◽  
Natalie Claudio ◽  
Zihan Guo ◽  
Tahereh Ziglari ◽  
Ferdinando Pucci
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Molecular Mechanisms ◽  
Tumor Formation ◽  
Marker Selection ◽  
Particulate Antigen ◽  
Macrophage Subset ◽  
Migratory Cells ◽  
Anti Tumor Activity

Lymph nodes are key lymphoid organs collecting lymph fluid and migratory cells from the tissue area they survey. When cancerous cells arise within a tissue, the sentinel lymph node is the first immunological organ to mount an immune response. Sub-capsular sinus macrophages (SSMs) are specialized macrophages residing in the lymph nodes that play important roles as gatekeepers against particulate antigenic material. In the context of cancer, SSMs capture tumor-derived extracellular vesicles (tEVs), a form of particulate antigen released in high amounts by tumor cells. We and others have recently demonstrated that SSMs possess anti-tumor activity because in their absence tumors progress faster. A comprehensive profiling of SSMs represents an important first step to identify the cellular and molecular mechanisms responsible for SSM anti-tumor activity. Unfortunately, the isolation of SSMs for molecular analyses is very challenging. Here, we combined an optimized dissociation protocol, careful marker selection and stringent gating strategies to highly purify SSMs. We provide evidence of decreased T and B cell contamination, which allowed us to reveal the gene expression profile of this elusive macrophage subset. Squamous cell carcinomas induced an increase in the expression of Fc receptors, lysosomal and proteasomal enzymes in SSMs. Imaging of mouse and patient lymph nodes confirmed the presence of the top differentially expressed genes. These results suggest that SSMs respond to tumor formation by upregulating the machinery necessary for presentation of tumor particulate antigens to B cells.

scholarly journals CYTOLOGICAL EVIDENCE FOR A RELATIONSHIP BETWEEN NORMAL HEMATOPOIETIC COLONY-FORMING CELLS AND CELLS OF THE LYMPHOID SYSTEM

1968 ◽  
Vol 127 (3) ◽  
pp. 455-464 ◽  
Author(s):  
A. M. Wu ◽  
J. E. Till ◽  
L. Siminovitch ◽  
E. A. McCulloch
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Immunological Response ◽  
Cytological Evidence ◽  
Hematopoietic System ◽  
Chromosome Marker ◽  
Common Precursor ◽  
The Relationship

The relationship between hematopoietic colony-forming stem cells and cells in the thymus and lymph nodes of unirradiated mice has been investigated using a chromosome-marker technique. It was found that a high proportion of cells in the thymus may belong to the same clone as normal hematopoietic colony-forming cells. It was also found that cells belonging to the same clone as colony-forming cells may reach the lymph nodes, and that nodes containing such cells can participate in an immunological response against sheep red cells. Either the precursors of cells in thymus and lymph node are identical with hematopoietic colony-forming cells, or they are both descendants of a common precursor which has not yet been identified. The results are compatible with the view that cells of the hematopoietic system and the immune system may be derived from the same stem cell.

scholarly journals Screening and identification of key candidate genes and pathways in myelodysplastic syndrome by bioinformatic analysis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8162
Author(s):  
Ying Le
Keyword(s):  
Gene Expression ◽  
Myelodysplastic Syndrome ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Hematologic Malignancy ◽  
Expression Profiles ◽  
Interaction Network ◽  
Functional Enrichment ◽  
Hematopoietic Stem ◽  
Diagnosis And Prognosis

Myelodysplastic syndrome (MDS) is a heterogeneous hematologic malignancy derived from hematopoietic stem cells and the molecular mechanism of MDS remains unclear. This study aimed to elucidate potential markers of diagnosis and prognosis of MDS. The gene expression profiles GSE19429 and GSE58831 were obtained and downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in MDS were screened using GEO2R and overlapped DEGs were obtained with Venn Diagrams. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analyses, protein–protein interaction network establishment and survival analyses were performed. Functional enrichment analysis indicated that these DEGs were significantly enriched in the interferon signaling pathway, immune response, hematopoietic cell lineage and the FOXO signaling pathway. Four hub genes and four significant modules including 25 module genes were obtained via Cytoscape MCODE. Survival analysis showed that the overall survival of MDS patients having BLNK, IRF4, IFITM1, IFIT1, ISG20, IFI44L alterations were worse than that without alterations. In conclusion, the identification of these genes and pathways helps understand the underlying molecular mechanisms of MDS and provides candidate targets for the diagnosis and prognosis of MDS.

scholarly journals STUDIES ON THE IMMUNOLOGICAL RESPONSE TO FOREIGN TUMOR TRANSPLANTS IN THE MOUSE

1955 ◽  
Vol 102 (2) ◽  
pp. 199-204 ◽  
Author(s):  
P. Andreini ◽  
M. L. Drasher ◽  
N. A. Mitchison
Keyword(s):  
Protein Synthesis ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Nitrogen Content ◽  
Immunological Response ◽  
Protein Nitrogen ◽  
Transplantable Tumors ◽  
Lymph Node Cells ◽  
Draining Lymph Nodes

A study was made of variation in weight of the host lymph nodes, spleen, and thymus, after implantation of transplantable tumors in susceptible and See PDF for Structure non-susceptible hosts. The lymph nodes and spleens of non-susceptible hosts increased in weight during the period when the organs were participating in the immunological response, though an increase also took place in susceptible hosts. Variations in protein nitrogen and pentose- and desoxypentosenucleic acid of the draining lymph nodes of non-susceptible mice were also studied. The protein nitrogen content increased with the weight of the nodes. Increase in the PNA/DNA ratio occurred while the lymph node cells were engaged in production of antibody. Increase in the PNA/DNA ratio was interpreted as an increase in PNA per cell, and therefore of the rate of protein synthesis.

scholarly journals Uterine lymphangiography: comparison of two methods for locating the medial iliac lymph node

2014 ◽  
Vol 34 (11) ◽  
pp. 1121-1126 ◽  
Author(s):  
Rebeca C. Justino ◽  
Guilherme S. Cardoso ◽  
Luiz G.C. Trautwein ◽  
Gabriel T. Dessunti ◽  
Deise V. Oliveira ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Physiological Status ◽  
Iliac Lymph Node ◽  
Diagnosis And Prognosis ◽  
Patent Blue ◽  
Therapeutic Measures ◽  
Patent Blue V ◽  
The Relationship

Different methods for lymphatic mapping in dogs, such as infusing tissues with vital dyes or radioactive substances, have been studied, aiming at the early detection of lymph node metastasis. Thus, one could anticipate therapeutic measures and, consequently, prolong the survival and improve the quality of life of the patients. The objectives of this experiment were to locate the nodes responsible for draining the uterine body and horns and to try to establish the relationship between the uterus and the medial iliac lymph nodes to contribute to the early diagnosis and prognosis of uterine disorders. We studied 15 female dogs divided into two groups (5 dead and 10 intraoperative ovariohysterectomy bitches). The dye used was patent blue V (Patent Bleu V®). It was observed that the iliac lymph node chain receives much of the uterine (horns) drainage. This method should be considered for safer studies of uterine sanity. This information suggests that evaluating these lymph nodes will allow correlating changes in their physiological status with uterine pathologies.

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