Similar Datasets
Project description:Purpose: Characterization of the gene expression profile and TCR profile of CD4+CD26- T cells from CTCL to understand the cell of origin
2023-08-16 | GSE207679 | GEO
Project description:Cutaneous T-cell lymphomas (CTCL) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult due to a clinical and histological resemblance to benign inflammatory skin diseases. To address if microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we study miRNA expression in 199 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays we show that the most induced- (miR-326, miR-663b, miR-711) and repressed- (miR-203, miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Q-RT-PCR analysis of 104 patients with CTCL and benign skin disorders validates differential expression of 4 out of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A q-RT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity, sensitivity, and a classification accuracy of 95% indicating that miRNAs have a high diagnostic potential in CTCL.
2011-11-22 | GSE31408 | GEO
Project description:Cutaneous T-cell lymphomas (CTCL) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult due to a clinical and histological resemblance to benign inflammatory skin diseases. To address if microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we study miRNA expression in 199 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays we show that the most induced- (miR-326, miR-663b, miR-711) and repressed- (miR-203, miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Q-RT-PCR analysis of 104 patients with CTCL and benign skin disorders validates differential expression of 4 out of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A q-RT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity, sensitivity, and a classification accuracy of 95% indicating that miRNAs have a high diagnostic potential in CTCL. miRNA microarray. From each sample 100 ng of total RNA was labeled with Hy3 fluorescent dye using the miRCURY LNA Array power labeling kit (Exiqon, Denmark). All samples were labeled the same day with the same master mix, in order to minimize technical variation. The Hy3-labelled samples were hybridized to miRCURY LNA arrays (v11.0) (Exiqon, Denmark), containing capture probes targeting all human miRNAs registered in the miRBASE version 15.0 at the Sanger Institute. The hybridization was performed overnight at 56°C according to manufacturer specifications using a Tecan HS4800 hybridization station (Tecan, Austria). Since it was not possible to hybridize all arrays in one go, samples were randomly split into 5 batches as to minimize day to day variation in the hybridization process. After hybridization the microarray slides were scanned using an Agilent G2565BA Microarray Scanner System (Agilent Technologies, Inc., USA) at 5µm resolution, and the resulting TIFF images were analyzed using the ImaGene 8.0 software on standard settings (BioDiscovery, Inc., USA).
2011-11-22 | E-GEOD-31408 | biostudies-arrayexpress
Project description:Cutaneous T cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing three patient clusters. Two clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB subjects appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated with a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower stage/treatment responsive versus higher stage/treatment resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted. Experiment Overall Design: 63 skin biopsies from patients with different stages of disease were selected for RNA extraction and hybridization on Affymetrix microarrays
2008-06-16 | E-GEOD-9479 | biostudies-arrayexpress
Project description:Cobomarsen (MRG‐106), an oligonucleotide inhibitor of miR‐155, has been evaluated in a clinical phase 1/2 trial for CTCL. We used lesional skin samples from 6 CTCL patients to identify the critical pathways affected by miR‐155 inhibition in CTCL.
2021-08-04 | GSE181117 | GEO
Project description:Cutaneous T cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing three patient clusters. Two clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB subjects appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated with a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower stage/treatment responsive versus higher stage/treatment resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted. Keywords: disease state analysis
2007-11-01 | GSE9479 | 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:Cutaneous T cell lymphoma (CTCL) is characterized by the proliferation of CD4+ T cells in a background of chronic inflammation, where malignant CTCL cells escape immune surveillance and are not eliminated. To study how miRNAs (miRs) regulate T cell exhaustion in this disease, we performed miRseq analysis, qRT-PCR, and in situ hybridization on 45 primary CTCL samples, 3 healthy skin samples, and CTCL cell lines, identifying miR-155-5p, -130b-3p and -21-3p. Moreover, miR-155-5p, -130b-3p, and -21-3p positively correlated with immune checkpoint gene expression in lesional skin samples and were enriched in the IL6/JAK/STAT signaling pathway by gene set enrichment analysis.
2021-12-07 | GSE181118 | GEO
Project description:Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing T cells. A subgroup of patients develops large cell transformation with progression to an aggressive lymphoma and with poor survival. We aimed to study the transformed CTCL (tCTCL) ecosystem using integrative approaches spanning whole-exome sequencing (WES), single-cell RNAseq, and immune profiling in a unique cohort of 56 patients with tCTCL
2024-07-12 | GSE272005 | GEO
Project description:Increasing evidences support a potential role for the Signal Transducer and Activator of Transcription-3 (STAT3) as a tumor driver in cutaneous T-cell lymphoma (CTCL). However, the mechanisms leading to STAT3 pathway activation in CTCL and how STAT3 activation contributes to lymphomagenesis remains primarily not enough explored. Recently, we found that miR-124, a known STAT3 regulator in cancer, is robustly silenced in Mycosis Fungoides (MF) tumor-stage and CTCL cell lines and we have herein studied whether deregulation of miR-124 contributes to activate STAT3 pathway in CTCL. Material and Methods: DNA methylation status of miR-124 and its expression levels in response to the DNA-demethylating agent azacitidine were evaluated in CTCL cell lines by pyrosequencing analysis. CTCL cell lines were transient transfected with a lentiviral vector encoding miR-124 and transfected cells were analyzed for phosphorylated STAT3 (P-STAT3) levels. The impact on STAT3 signaling was evaluated using expression microarray on CTCL cell lines in both conditions, miR-124 absent (malignant condition) versus miR-124 expressed (lentiviral transduction). Results: A significant promoter methylation and silencing of miR-124 in MF tumor samples and CTCL cell lines was detected. DNA methylation levels of miR-124 in CTCL cell lines were restored (and subsequently miR-124 were overexpressed) after DNA demethylation. Ectopic lentiviral expression of miR-124 downregulated STAT3 in the different CTCL cell lines. Genes differentially expressed regarding miR-124 regulation in CTCL cell lines indicated impact on known cell survival and function pathways and, particularly, intervention on miR-124 expression modulated different STAT3 pathway components. Conclusions: Our study deciphers a novel epigenetic mechanisms regulating STAT3 pathway in CTCL. This might contribute to a better understanding the molecular basis in CTCL development. Deregulation of STAT3 seems to have a major impact on cell survival in CTCL cell lines indicating the potential interest of targeting STAT3 with specific therapies.
2020-12-31 | GSE130809 | GEO