RUNX2 as a novel Biomarker for early identification of Patients Progressing to Advanced-Stage Mycosis Fungoides
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE275677 | GEO | 2024/09/13
REPOSITORIES: GEO
Similar Datasets
Project description:Background: In early-stage mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, limited skin involvement with patches and plaques is associated with a favorable prognosis. Nevertheless, approximately 20-30% of cases progress to tumors or erythroderma, resulting in poor outcome. At present, factors contributing to this switch from indolent to aggressive disease are only insufficiently understood. Methods: In patients with advanced-stage MF, we compared patches with longstanding history to newly developed plaques and tumors by using single-cell RNA sequencing, and compared results with early-stage MF as well as nonlesional MF and healthy control skin. Results: Despite considerable inter-individual variability, lesion progression was uniformly associated with downregulation of the tissue residency markers CXCR4 and CD69, the heat shock protein HSPA1A, the tumor suppressors and immunoregulatory mediators ZFP36 and TXNIP, and the interleukin 7 receptor (IL7R) within the malignant clone, but not in benign T cells. This phenomenon was not only found in conventional TCR-αβ MF, but also in a case of TCR-γδ MF, suggesting a common mechanism across MF subtypes. Conversely, malignant cells in clinically unaffected skin from MF patients showed upregulation of these markers. Conclusions: Our data reveal a specific panel of biomarkers that might be used for monitoring MF disease progression. Altered expression of these genes may underlie the switch in clinical phenotype observed in advanced-stage MF.
2021-09-13 | GSE173205 | GEO
Project description:Purified B cells from untreated CLL patients were tested at two time points by liquid chromatography-tandem mass spectrometry. Patients included in the study evolved to either progressive or stable disease . Samples were tested for both groups at diagnosis (Stage Binet A for all patients included), 3 years after diagnosis for the stable disease patients and at the time of progression to stage Binet B/C for those who progressed.
2021-06-01 | MSV000087556 | MassIVE
Project description:<p>Mycosis fungoides (MF) is a common extranodal T-cell lymphoma primarily arising in the skin. In early disease stages, MF presents as skin patches and plaques that in some cases may progress to tumor and disperse to lymph nodes and other internal organs. The 10-year overall survival is 50% in advanced stages. Early diagnosis is difficult as the histology overlaps with features of inflammatory skin diseases. Even when the diagnosis is established, there are no prognostic markers that predict whether the disease will be aggressive or indolent. Lastly, there are no curative treatments and MF will invariably relapse, even after aggressive chemotherapy. The disease is a diagnostic, prognostic and therapeutic challenge. The main objective of this study is to address the question of tumor heterogeneity in MF. To date, MF is considered to be monoclonal, derived from a transformed, mature memory T-cell. However, clinical observations and preliminary data suggest that MF comprises multiple subclones, which may be of importance for understanding disease evolution and resistance to therapy. We plan to address this objective using Whole Exome Sequencing (WES) of MF tissue prepared by laser microdissection (LMD).</p>
| phs001877 | dbGaP
Project description:Cursons2015 - Regulation of ERK-MAPK
signaling in human epidermis
Model comparing the abundance of
phosphorylated MAPK signalling proteins and calcium signalling in
the epidermis.
This model is described in the article:
Regulation of ERK-MAPK
signaling in human epidermis.
Cursons J, Gao J, Hurley DG, Print
CG, Dunbar PR, Jacobs MD, Crampin EJ.
BMC Syst Biol 2015; 9: 41
Abstract:
The skin is largely comprised of keratinocytes within the
interfollicular epidermis. Over approximately two weeks these
cells differentiate and traverse the thickness of the skin. The
stage of differentiation is therefore reflected in the
positions of cells within the tissue, providing a convenient
axis along which to study the signaling events that occur in
situ during keratinocyte terminal differentiation, over this
extended two-week timescale. The canonical ERK-MAPK signaling
cascade (Raf-1, MEK-1/2 and ERK-1/2) has been implicated in
controlling diverse cellular behaviors, including proliferation
and differentiation. While the molecular interactions involved
in signal transduction through this cascade have been well
characterized in cell culture experiments, our understanding of
how this sequence of events unfolds to determine cell fate
within a homeostatic tissue environment has not been fully
characterized.We measured the abundance of total and
phosphorylated ERK-MAPK signaling proteins within
interfollicular keratinocytes in transverse cross-sections of
human epidermis using immunofluorescence microscopy. To
investigate these data we developed a mathematical model of the
signaling cascade using a normalized-Hill differential equation
formalism.These data show coordinated variation in the
abundance of phosphorylated ERK-MAPK components across the
epidermis. Statistical analysis of these data shows that
associations between phosphorylated ERK-MAPK components which
correspond to canonical molecular interactions are dependent
upon spatial position within the epidermis. The model
demonstrates that the spatial profile of activation for
ERK-MAPK signaling components across the epidermis may be
maintained in a cell-autonomous fashion by an underlying
spatial gradient in calcium signaling.Our data demonstrate an
extended phospho-protein profile of ERK-MAPK signaling cascade
components across the epidermis in situ, and statistical
associations in these data indicate canonical ERK-MAPK
interactions underlie this spatial profile of ERK-MAPK
activation. Using mathematical modelling we have demonstrated
that spatially varying calcium signaling components across the
epidermis may be sufficient to maintain the spatial profile of
ERK-MAPK signaling cascade components in a cell-autonomous
manner. These findings may have significant implications for
the wide range of cancer drugs which therapeutically target
ERK-MAPK signaling components.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000659.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000659 | BioModels
Project description:We report ileal gene expression at diagnosis in a cohort of 210 treatment-naïve patients of pediatric Crohn's disease and 35 non-IBD controls from the RISK study. After three years of follow-up after diagnosis, 27 of the CD patients progressed to complicated disease (B2 and/or B3). We aim to test whether Transcriptional Risk Scores helps to distinguish between patient subgroups, improving the predictive power gained from Genetic Risk Scores.
2017-06-20 | GSE93624 | GEO
Project description:Mycosis fungoides (MF) is the most common T-cell lymphoma in cutaneous malignant lymphoma, which may involve multiple organs in the advanced stage with a poor prognosis. Till now, early identification of the disease is still urgent and also there is no optimal therapy for advanced MF. In the present study, quantitative proteomic analyses (Label Free Quantitation, LFQ) and a parallel reaction monitoring (PRM) assay were applied in tissue samples of different stages of MF and the control group, so as to conduct preliminary molecular analysis of the significantly expressed proteins which may involve in the pathogenesis of the disease. The results revealed that genes and proteins implicated in DNA replication initiation, nucleosome assembly, cell adhesion activity, together with the cellular component and molecules that connecting extracellular region part may be involved in the pathogenesis and metastasis of MF. Some special proteins expressed obviously differently from the early to advanced stage of MF, indicating that they may be the key molecules for the progression of the disease. We believe that proteomics is a powerful tool to identify potential biomarkers for diagnosis and these molecules may be promising therapeutic targets for MF. For that, further studies are still needed.
2021-11-23 | PXD027714 | Pride
Project description:CTCLs are a group of non-Hodgkin lymphomas, with non-aggressive forms (Mycosis fungoides (MF)) initially presenting with features of cutaneous eczema or psoriasis, posing a challenge for clinical and histological diagnosis. Using spatial transcriptomics, we hope to delineate the molecular signatures of CTCL to provide novel avenues for diagnostics and therapies.
2024-04-01 | E-MTAB-13614 | biostudies-arrayexpress
Project description:Background: Malignant clones of primary cutaneous T-cell lymphomas (CTCL) can show a CD4+, CD8+ or T-cell receptor γδ+ phenotype, but their individual impact on tumor biology and skin lesion formation remains ill-defined. We perform a comprehensive molecular characterization of CD4+ vs. CD8+ and TCR-γ/δ+ CTCL lesions. Methods: We performed scRNA-seq of 18 CTCL skin biopsies to compare classic CD4+ advanced-stage mycosis fungoides (MF) with TCR-γ/δ+ MF and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (Berti’s lymphoma). Results: Malignant clones of TCR-γ/δ+ MF and Berti’s lymphoma showed similar clustering patterns distinct from CD4+ MF, along with increased expression of cytotoxic markers such as NKG7, CTSW, GZMA, and GZMM. Only advanced-stage CD4+MF clones expressed central memory T-cell markers (SELL, CCR7, LEF1), alongside B1/B2 blood involvement, whereas TCR-γ/δ+ MF and Berti’s lymphoma harbored a more tissue-resident phenotype (CD69, CXCR4, NR4A1) without detectable cells in the blood. CD4+ MF and TCR-γ/δ+ MF skin lesions harbored strong type 2 immune activation across myeloid cells, while Berti’s lymphoma was more skewed towards type 1 immune responses. Both CD4+ MF and TCR-γ/δ+ MF lesions showed upregulation of keratinocyte hyperactivation markers such as S100As and KRT16 genes. This increase was entirely absent in Berti’s lymphoma, possibly reflecting an aberrant keratinocyte response to invading tumor cells, that could contribute to the formation of the typical ulcero-necrotic lesions within this entity. Conclusions: Our scRNAseq profiling study reveals specific molecular patterns associated with distinct CTCL subtypes.
2024-10-24 | GSE266862 | GEO
Project description:Purpose: The heterogeneity of tumor cells presents a major challenge to cancer diagnosis and therapy. Cutaneous T cell lymphomas (CTCL) are a group of T lymphocyte malignanciesthat primarily affect skin. Lack of highly specific markers for malignant lymphocytes prevents early diagnosis, while only limited treatment options are available for patients with advanced-stage CTCL.Droplet-basedsingle-cell transcriptome analysis of CTCL skin biopsiesopens avenues for dissecting patient-specificT lymphocyte heterogeneity, providing a basis for identifying specific markers for diagnosis and cure of CTCL. Experimental Design: Single-cell RNA-sequencing was performed by Droplet-based sequencing (10X Genomics), focusing on 14,056 CD3+lymphocytes (448 cells from normal and 13,608 cells from CTCL skin samples) from skin biopsies of 5 patients with advanced-stage CTCL and 4 healthy donors.Protein expression of identified genes was validated in advanced-stage CTCL skin tumors byimmunohistochemistry and confocal immunofluorescence microscopy. Results: Our analysis revealed a large inter- and intra-tumor gene expression heterogeneity in the T lymphocyte subset, as well as a common gene expression signature in highly proliferating lymphocytes that was validated in multiple advanced-stage skin tumors. In addition, we established the immunological state of reactive lymphocytes and found heterogeneity in effector and exhaution programs across patient samples. Conclusions: Single-cell analysis of CTCL skin tumor samples reveals patient-specific landscapes of malignant and reactive lymphocytes within the local microenvironment of each tumor, giving anunprecedented view of lymphocyte heterogeneity and identifying tumor-specific molecular signatures, withimportant implications for diagnosis and personalized disease treatment.
2019-05-10 | GSE128531 | GEO
Project description:Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma, arising from clonal expansion of transformed skin-homing memory T cells. However, the lack of specific markers for malignant lymphocytes prevents distinguishing them from benign T cells in the tumor microenvironment (TME) of MF, thus delaying diagnosis and development of specific treatment, which results in poor clinical outcomes. Here we employed recent advances in single-cell RNA-sequencing to establish the transcriptome of expanded T-cell clones directly in advanced-stage MF skin tumors, allowing the transcriptional profiles of malignant and reactive T lymphocytes to be distinguished. Our analysis identified multiple non-overlapping expanded T-cell clonotypes within individual MF tumors, which included malignant and reactive clones. Heterogeneity among samples was observed not only in the number of expanded clonotypes but also in their TCR specificity and gene expression. While patient-specific tumorigenic pathways were up-regulated by the malignant clones, we also identified a common gene expression that included genes associated with cancer cell metabolism, de novo nucleotide biosynthesis, and invasion. Most non-malignant clones originated from CD8+ T cells and commonly presented an exhausted immune phenotype and activated Th1/Th2 pathways. While non-clonal infiltrating CD4+ and CD8+ lymphocytes from all tumors shared anti-inflammatory and immunosuppressive pathways, patient-specific mechanisms included the TNFR2 signaling cascade, ferroptosis, and cytotoxic pathways by gamma/delta T cells. Thus, scRNAseq reveals new insights in MF pathogenesis by providing an unprecedented report of the transcriptomes of malignant and reactive T cells in the TME of individual patients and offers novel prospective targets for personalized therapy.
2022-06-01 | GSE182861 | GEO