RUNX2 as a novel Biomarker for early identification of Patients Progressing to Advanced-Stage Mycosis Fungoides
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE275677 | GEO | 2024/09/13
REPOSITORIES: GEO
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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:Mycosis fungoides (MF) is the most common and best studied of cutaneous T-cell lymphoma (CTCL). Three clinical cutaneous stages have been described (patch, plaque and tumor) as the disease progress developing also the disease lymph node, peripheral blood or systemic involvement in late stages. Clinical and pathologic diagnosis of early MF stages (patch and plaque) is difficult as its morphologic similarity to inflammatory dermatoses and low proportion of tumoral cells.
2018-06-21 | GSE109421 | GEO
Project description:In the epidermis, CCR4, CCR6, CCL20 and CCL27 were higher in ATLL than in MF. We obtained the epidermal samples from MF (n=5) and ATLL (n=5) with the aid of laser microdissection. Complementary RNA amplification were used for gene expression profiling by microarray analysis. We compaired MF with ATLL in epidermis. We obtained the epidermal dermal samples from MF (n=3) and ATLL (n=3) with the aid of laser microdissection. Complementary RNA amplification were used for gene expression profiling by microarray analysis. We compaired MF with ATLL in dermis.
2012-09-06 | E-GEOD-40639 | biostudies-arrayexpress
Project description:Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. While initially restricted to the skin, malignant cells can appear in blood, bone marrow and secondary lymphoid organs in later disease stages. However, only little is known about phenotypic and functional properties of malignant T cells in relationship to tissue environments over the course of disease progression. We thus profiled the tumor micromilieu in skin, blood and lymph node in a patient with advanced MF using single-cell RNA sequencing combined with V-D-J T-cell receptor sequencing. In skin, we identified clonally expanded T-cells with characteristic features of tissue-resident memory T-cells (TRM, CD69+CD27-NR4A1+RGS1+AHR+). In blood and lymph node, the malignant clones displayed a transcriptional program reminiscent of a more central memory-like phenotype (KLF2+TCF7+S1PR1+SELL+CCR7+), while retaining tissuehoming receptors (CLA, CCR10). The skin tumor microenvironment contained potentially tumor-permissive myeloid cells producing regulatory (IDO1) and Th2-associated mediators (CCL13, CCL17, CCL22). Given their expression of PVR, TNFRSF14 and CD80/CD86, they might be under direct control by TIGIT+CTLA4+CSF2+TNFSF14+ tumor cells. In sum, this study highlights the adaptive phenotypic and functional plasticity of MF tumor cell clones. Thus, the TRM-like phenotype enables long-term skin residence of MF cells. Their switch to a TCM-like phenotype with persistent skin homing molecule expression in the circulation might explain the multi-focal nature of MF.
2021-04-13 | GSE165623 | GEO
Project description:Malignant T lymphocyte proliferation in mycosis fungoides (MF) is largely restricted to the skin, implying that malignant cells are dependent on their specific cutaneous tumor microenvironment (TME), including interactions with non-malignant immune and stromal cells, cytokines, and other immunomodulatory factors. To explore these interactions, we performed a comprehensive transcriptome analysis of the TME in advanced-stage MF skin tumors by single-cell RNA sequencing. Our analysis identified cell-type compositions, cellular functions, and cell-cell interactions in the MF TME that were distinct from those from healthy skin and benign dermatoses. While patterns of gene expression were common amongst patient samples, high transcriptional diversity was also observed in immune and stromal cells, with dynamic interactions and crosstalk between these cells and malignant T lymphocytes. This heterogeneity mapped to processes such as cell trafficking, matrix interactions, angiogenesis, immune functions, and metabolism that affect cancer cell growth, migration and invasion, as well as anti-tumor immunity. By comprehensively characterizing the transcriptomes of immune and stromal cell within the cutaneous microenvironment of individual MF tumors, we have identified patterns of dysfunction common to all tumors that represents a resource for identifying candidates with therapeutic potential as well as patient-specific heterogeneity that has important implications for personalized disease management.
2023-11-21 | GSE206123 | GEO
Project description:In the epidermis, CCR4, CCR6, CCL20 and CCL27 were higher in ATLL than in MF.
2012-09-06 | GSE40639 | GEO
Project description:Primary cutaneous T-cell lymphoma (CTCL) is responsible for two-thirds of cutaneous lymphoma cases. Mycosis fungoides (MF), the most common subtype of CTCL comprises approximately 60% of CTCLs. Due to the similar clinical features of MF and inflammatory diseases such as eczema and psoriasis, early-stage MF can easily be misdiagnosed as chronic inflammatory dermatoses, posing a diagnostic challenge to the dermatologist. Early-stage MF is characterized by a favorable prognosis with long-term survival similar to or slightly lower than that of age-matched healthy people, with a 5-year survival between 88% and 100%. In contrast, advanced-stage MF shows aggressive progression, and the median survival time of patients with lymph node and visceral involvement is only 13 months. Therefore, it is important to achieve early diagnosis to improve prognosis, yet there are few specific biomarkers for the early diagnosis and prognosis of MF. In this study, we described the pathological features of MF during the early and advanced stages through proteomics technology, providing clues for the pathogenesis of MF as well as biomarkers for malignant tumors in the early stage. More importantly, diagnostic biomarkers of early-stage MF were identified by comparing the proteomic characteristics of early-stage MF and inflammatory diseases, with the goal of preventing delayed therapy due to misdiagnosis.
2020-11-28 | PXD022798 |
Project description:Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is a malignancy of mature, skin-homing T cells. Sézary syndrome (Sz) is often considered to represent a leukemic phase of MF. In this study the pattern of numerical chromosomal alterations in MF tumor samples was defined using array-based CGH; simultaneously gene expression was analyzed using microarrays. Highly recurrent chromosomal alterations in MF include copy number gain of 7q36, 7q21-7q22 and loss of 5q13 and 9p21. This pattern characteristic of MF differs markedly from chromosomal alterations observed in Sz. Integration of data from array-based CGH and gene expression analysis yielded several candidate genes with potential relevance in the pathogenesis of MF. We confirmed that the FASTK and SKAP1 genes, residing in loci with recurrent gain, demonstrated increased expression. The RB1 and DLEU1 tumor suppressor genes showed diminished expression associated with loss. In addition, it was found that presence of chromosomal alterations on 9p21, 8q24 and 1q21-1q22 was associated with poor prognosis in patients with MF. This study provides novel insight into genetic alterations underlying MF. Furthermore, our analysis uncovered genomic differences between MF and Sz, which suggest that the molecular pathogenesis and therefore therapeutic requirements of these CTCLs may be distinct. To identify candidate oncogenes and tumor suppressor genes residing in chromosomal regions with recurrent copy number alteration in MF. To this end chromosomal alteration and gene expression patterns of 22 MF tumor samples were integrated to determine which genes located in minimal common regions (MCRs) with CNA demonstrated dysregulated expression associated with chromosomal alteration Keywords: aCGH and gene expression integration 22 tumors for aCGH and gene expression
2008-09-29 | E-GEOD-12902 | biostudies-arrayexpress
Project description:Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is a malignancy of mature, skin-homing T cells. Sézary syndrome (Sz) is often considered to represent a leukemic phase of MF. In this study the pattern of numerical chromosomal alterations in MF tumor samples was defined using array-based CGH; simultaneously gene expression was analyzed using microarrays. Highly recurrent chromosomal alterations in MF include copy number gain of 7q36, 7q21-7q22 and loss of 5q13 and 9p21. This pattern characteristic of MF differs markedly from chromosomal alterations observed in Sz. Integration of data from array-based CGH and gene expression analysis yielded several candidate genes with potential relevance in the pathogenesis of MF. We confirmed that the FASTK and SKAP1 genes, residing in loci with recurrent gain, demonstrated increased expression. The RB1 and DLEU1 tumor suppressor genes showed diminished expression associated with loss. In addition, it was found that presence of chromosomal alterations on 9p21, 8q24 and 1q21-1q22 was associated with poor prognosis in patients with MF. This study provides novel insight into genetic alterations underlying MF. Furthermore, our analysis uncovered genomic differences between MF and Sz, which suggest that the molecular pathogenesis and therefore therapeutic requirements of these CTCLs may be distinct. To identify candidate oncogenes and tumor suppressor genes residing in chromosomal regions with recurrent copy number alteration in MF. To this end chromosomal alteration and gene expression patterns of 22 MF tumor samples were integrated to determine which genes located in minimal common regions (MCRs) with CNA demonstrated dysregulated expression associated with chromosomal alteration Keywords: aCGH and gene expression integration
2008-09-30 | GSE12902 | GEO
Project description:Mycosis Fungoides (MF) is typically characterized by a mature CD4+ memory T-cell phenotype, and regarded as a helper T-cell (Th)2-skewed disease. Here, using skin samples from MF (n=21), healthy volunteers (n=17), atopic dermatitis (n=17), and psoriasis (n=9), we performed RT-PCR to show highest interleukin (IL)-32 mRNA expression in MF compared to benign inflammatory diseases, and its increasing expression with disease progression. By immunohistochemistry and immunofluorescence, we confirmed IL-32 protein expression by numerous CD3+CD4+ T-cells and some epidermotropic T-cells in MF lesions. IL-32 is expressed by MyLa cells (MF cell line) and promoted their proliferation and viability in a dose-dependent fashion. IL-32-treated MyLa and HH cells (CTCL cell line) showed upregulation of cell proliferation and survival genes. Of major 'polar' T-cell cytokines, only IFN-γ mRNA increases with MF progression and positively correlates with IL-32 mRNA expression levels. Th2 cytokines do not show consistent increases with MF progression nor positive correlation with IL-32 mRNA expression levels. Furthermore, by flow cytometry, IL-32 production by circulating activated T-cells in healthy individulas was found in IFN-γ+ and IFN-γ- cells but not in IL-4+ or IL-13+ cells. In conclusion, we identified IL-32+ cells as likely tumor cells in MF, and clearly showed that IL-32 mRNA expression levels increase with MF progression. We found that IL-32 mRNA expression levels in MF are significantly higher than those in other skin diseases, and that some IL-32+ T-cells are independent from defined Th subsets. Thus IL-32 may play a unique role in MF progression as an autocrine cytokine.
2014-12-31 | GSE58033 | GEO