Gene expression profilling of metastatic melanoma cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE16404 | GEO | 2010/01/02
SECONDARY ACCESSION(S): PRJNA116299
REPOSITORIES: GEO
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Project description:Melanoma can progress rapidly from a slow-growing surgically curable lesion to aggressive metastatic disease, with high mortality and poor response to current therapies. The mechanisms underlying melanoma progression and resistance to therapeutic agents are not well understood. There are few treatment options for melanoma once it has metastasized, and new biomarkers that aid diagnosis, predict clinical outcome, and suggest new therapies are required. This aim of this study was to invesigate the molecular basis of melanoma biology and heterogeneity by defining genomic characteristics that correlated with tumour phenotype in a novel panel of 25 cell lines derived largely from New Zealand patients with metastatic melanoma. The goals of this study were to (i) stratify melanoma cell lines by using global gene expression profiling ; (ii) correlate gene expression profiles with invasive potential; and (iii) identify new prognostic markers and therapeutic targets that might aid clinical cancer diagnosis and management. Two-colour spotted oligonucleotide microarrays were used to measure global gene expression in metastatic melanoma cell lines against a common universal reference. Biological replication was achieved by performing replicate arrays on a subset of randomly selected cell lines, in which the replicate total RNA samples were isolated from different vials of cells at different passage numbers, grown by different researchers, and often in different laboratories. Further, NZM01 and NZM02 were derived from different tumours from the same patient at different surgeries, and NZM07.2 and 07.4 were derived from the NZM07 cell line. The array hybridisations were peformed in three batches. Technical replication was achieved by using intra- and inter-batch replicates with different RNA samples from 6/25 of the cell lines: NZM04, 2 x batch 1, 1 x batch 2; NZM22, 2 x batch 1; NZM40, 1 x batch 1, 1 x batch 2; NZM06, 1 x batch 1, 1 x batch 3; NZM09, 1 x batch 1, 1 x batch 2; NZM15, 1 x batch 2, 1 x batch 3.
2010-05-16 | E-GEOD-16404 | biostudies-arrayexpress
Project description:Background: Timely diagnosis is important for successful treatment of cutaneous melanoma. Currently, Breslow tumor thickness and mitotic rate are used for malignant melanoma classification and prognosis, but these parameters can assess disease progression risk only to a certain degree. Therefore, there is a need for new melanoma protein biomarkers that would aid early and accurate diagnosis and prediction of their metastatic potential. Methodology and Findings: This retrospective case control study is based on proteomic profiling of formalin-fixed archival tissues of 31 early-stage head and neck cutaneous malignant melanoma samples using liquid chromatography / mass spectrometry. A melanoma proteomic profile was identified and protein expression levels were compared to the proteome profile of melanocytic naevi and correlated to established prognostic factors and disease-specific survival. In accordance with the American Joint Committee on Cancer guidelines, recursive partitioning multivariate analysis was used to identify potential biomarkers associated with metastatic potential of early-melanoma. Heterogeneous nuclear ribonucleoprotein M and heat shock protein 90 alpha were profiled as independent prognostic factors. Their elevated expression was clinically relevant for predicting an exceedingly high metastatic hazard ratio. These proteins were superior in estimating disease progression risk when compared to Breslow thickness and mitotic rate. Conclusions and Significance: Identification of biomarkers in early stage cutaneous head and neck melanoma is an important step towards predicting metastatic potential and prognosis of the disease. Clinical confirmation and further validation of the proteins identified in this study would provide a novel tool for identifying patients at risk for developing metastatic disease.
2019-11-27 | PXD015137 | Pride
Project description:The identification of novel tumor-specific markers may improve understanding of melanoma progression and prognostic accuracy. Whole genome expression profiling of 46 primary melanomas, 12 metastases, and 16 normal skin samples using Affymetrix U133 PLUS 2.0 array generated gene lists including both known and new melanoma genes. The molecular genetic alterations contributing to the pathogenesis of melanoma are incompletely defined and few independent prognostic features have been identified beyond the pathologic characteristics of the primary tumor. Early stage melanoma is frequently curable, in contrast to the inferior prognosis of melanomas with regional lymph nodes involvement and the incurability of distant metastatic disease. The identification of novel tumor-specific markers may improve our understanding of melanoma progression and prognostic accuracy. To find differentially expressed genes that can distinguish melanoma from normal tissue, we performed a whole genome expression profiling of 46 primary melanoma samples, 12 regional or distant metastases, and 16 normal skin samples using Affymetrix U133 2.0 Plus array. Our study generated lists of differentially expressed genes in melanoma and identified novel prognostic marker HMGA2. It is a novel, highly overexpressed melanoma gene associated with poor prognosis. The overexpression of HMGA2 is strongly associated with regional and distant metastases and serves as an independent predictor of disease-free survival and overall survival in melanoma. Melanoma samples were obtained through an IRB-approved protocol using informed consent at the University of Michigan Multidisciplinary Melanoma Clinic. A portion of pigmented lesions clinically suspicious for melanoma and known melanoma were sampled by punch biopsy at the time of excision. The punch biopsy was bisected; half was sent to for clinical diagnosis and the other half along with adjacent normal skin when available immediately snap-frozen in liquid nitrogen. Snap-frozen tissue was embedded in OCT (TissueTek) followed by frozen sectioning and H&E slide preparation. The slides were evaluated by dermatopathologist who identified areas with greater than 70% tumor cellularity, which were sampled for RNA extraction. Primary melanomas and melanoma metastases were derived from different patients. Metastatic samples included lymph nodes (n=8), subcutaneous soft tissue (n=2), spleen (n=1), and small intestine (n=1).
2012-06-07 | E-GEOD-15605 | biostudies-arrayexpress
Project description:The identification of novel tumor-specific markers may improve understanding of melanoma progression and prognostic accuracy. Whole genome expression profiling of 46 primary melanomas, 12 metastases, and 16 normal skin samples using Affymetrix U133 PLUS 2.0 array generated gene lists including both known and new melanoma genes. The molecular genetic alterations contributing to the pathogenesis of melanoma are incompletely defined and few independent prognostic features have been identified beyond the pathologic characteristics of the primary tumor. Early stage melanoma is frequently curable, in contrast to the inferior prognosis of melanomas with regional lymph nodes involvement and the incurability of distant metastatic disease. The identification of novel tumor-specific markers may improve our understanding of melanoma progression and prognostic accuracy. To find differentially expressed genes that can distinguish melanoma from normal tissue, we performed a whole genome expression profiling of 46 primary melanoma samples, 12 regional or distant metastases, and 16 normal skin samples using Affymetrix U133 2.0 Plus array. Our study generated lists of differentially expressed genes in melanoma and identified novel prognostic marker HMGA2. It is a novel, highly overexpressed melanoma gene associated with poor prognosis. The overexpression of HMGA2 is strongly associated with regional and distant metastases and serves as an independent predictor of disease-free survival and overall survival in melanoma.
2012-06-08 | GSE15605 | GEO
Project description:Both genomic and transcriptomic signatures have been developed to predict responses of metastatic melanoma to immune checkpoint blockade (ICB) therapies; however, most of these signatures were derived from pre-treatment biopsy samples. Here, we developed pathway-based signatures that predict response of metastatic melanoma to anti-PD1-based therapies in four independent datasets with RNAseq and clinical response data available for both pre- and on-treatment metastatic melanomas. We first identified pathway signatures that were significantly enriched in tumor specimens from anti-PD1 responders (R) compared to non-responders (NR) at pre-treatment and on-treatment time points, respectively. We also identified pathway signatures that were differentially expressed in pre-treatment versus on-treatment samples derived from R. Finally, we interrogated the capacity of the two types of signatures in predicting response of metastatic melanoma to anti-PD1 therapies in comparison with existing gene expression signatures. And we also investigated the effect of biopsy sites at the same biopsy time point on predictive performance of response to anti-PD1 therapy. Overall, we demonstrate that pathway-based signatures derived from on-treatment tumor specimens are highly predictive of response to anti-PD1 blockade therapies in patients with metastatic melanoma.
2021-08-15 | GSE168204 | GEO
Project description:Malignant melanoma is an aggressive heterogeneous disease for which new biomarkers for diagnosis and clinical outcome are needed. We investigated by array-CGH the presence of DNA gains and losses to provide better genomic profile of primary malignant melanoma and to explore the possibility to distinguish metastatic from non metastatic melanomas using this technology. High resolution array-CGH (Agilent Technologies, Palo Alto, CA), with more than 40.000 probes, has been used to analyze 20 frozen tissues of vertical growth phase primary melanoma with a minimum follow-up time of 36 months. Eight patients developed nodal metastatic disease and twelve did not. For results validation, 83 additional melanoma samples with similar clinical characteristics were analysed by FISH. DNA copy number aberrations (CNA) were observed in 19 out of 20 cases. The most frequent changes were complete or partial losses in chromosomes 9 (12 cases, 60%) and 10 (9 cases, 45%), partial gains or trisomies of chromosome 7 (10 cases, 50%); and monosomy of chromosome 19 (7 cases, 35%). Sixty-four recurrent aberrant regions (SORIs) were precisely delimited and used as variables for clustering. Unsupervised Cluster analysis allowed the segregation of samples into two genomic groups that naturally fitted with the metastatic condition of the cases. Four of these aberrant regions were chosen for their biological interest and were confirmed as aberrant using FISH technique on fixed paraffin embedded tissues. Conclusion: Supervised classification allowed obtaining aberrations useful to separate samples with different clinical outcome. Obtained results are useful to improve the knowledge about melanoma tumorigenesis but unfortunately cannot be used as a marker for metastatic progression. Experiment Overall Design: Comparative experiment: pheripheral blood pool of ten healthy female donors: CONTROL vs. 20 Primary Vertigal Growth Phase Melanoma samples.
2009-01-14 | E-GEOD-11109 | biostudies-arrayexpress
Project description:Here we report a novel role for H2A.Z.2 (H2AFV) as a mediator of cell proliferation and sensitivity to targeted therapies in malignant melanoma. While both H2A.Z.1 and H2A.Z.2 are highly expressed in metastatic melanoma and correlate with decreased patient survival, only H2A.Z.2 deficiency results in impaired cellular proliferation of melanoma cells, which occurs via a G1/S arrest. Integrated gene expression and ChIP-seq analyses revealed that H2A.Z.2 positively regulates E2F target genes, and that such genes acquire a distinct H2A.Z occupancy signature over the promoter and gene body in metastatic melanoma cells. We further identified the BET family member BRD2 as an H2A.Z-interacting protein in melanoma cells, and demonstrate that H2A.Z.2 silencing cooperates with BET inhibition to induce cell death. Expression levels for non tumorigenic (Melanocytes) and human melanoma cell line SKmel147, before and after JQ1 treatement
2015-07-01 | E-GEOD-68221 | biostudies-arrayexpress
Project description:Here we report a novel role for H2A.Z.2 (H2AFV) as a mediator of cell proliferation and sensitivity to targeted therapies in malignant melanoma. While both H2A.Z.1 and H2A.Z.2 are highly expressed in metastatic melanoma and correlate with decreased patient survival, only H2A.Z.2 deficiency results in impaired cellular proliferation of melanoma cells, which occurs via a G1/S arrest. Integrated gene expression and ChIP-seq analyses revealed that H2A.Z.2 positively regulates E2F target genes, and that such genes acquire a distinct H2A.Z occupancy signature over the promoter and gene body in metastatic melanoma cells. We further identified the BET family member BRD2 as an H2A.Z-interacting protein in melanoma cells, and demonstrate that H2A.Z.2 silencing cooperates with BET inhibition to induce cell death. Total RNA samples from SKmel147 melanoma cell line. Transcript levels were analyzed after control or H2AZ variant RNA interference.
2015-07-01 | E-GEOD-59026 | biostudies-arrayexpress
Project description:Here we report a novel role for H2A.Z.2 (H2AFV) as a mediator of cell proliferation and sensitivity to targeted therapies in malignant melanoma. While both H2A.Z.1 and H2A.Z.2 are highly expressed in metastatic melanoma and correlate with decreased patient survival, only H2A.Z.2 deficiency results in impaired cellular proliferation of melanoma cells, which occurs via a G1/S arrest. Integrated gene expression and ChIP-seq analyses revealed that H2A.Z.2 positively regulates E2F target genes, and that such genes acquire a distinct H2A.Z occupancy signature over the promoter and gene body in metastatic melanoma cells. We further identified the BET family member BRD2 as an H2A.Z-interacting protein in melanoma cells, and demonstrate that H2A.Z.2 silencing cooperates with BET inhibition to induce cell death. Cross-linked ChIP in SKmel147 melamoma cell line for E2F1 and BRD2
2015-07-01 | E-GEOD-68223 | biostudies-arrayexpress
Project description:The efficacy of immunotherapies in metastatic melanoma depends on a robust T cell infiltration. Consistently, defining cancer cell intrinsic mechanisms mediating T cell exclusion and immune resistance is crucial. The EMT inducing transcription factor ZEB1 is a major regulator of melanoma cell plasticity, driving resistance to MAPK targeted therapies. Here, by analyzing the immune infiltrates of a cohort of melanoma patients, we demonstrate that high ZEB1 expression in tumor cells is associated with a decrease in CD8+ T lymphocyte infiltration, independently of beta-catenin pathway activation. Moreover, gain- or loss-of-function experiments in melanoma mouse models show that ZEB1 regulates tumor growth by controlling CD8+ T cell recruitment, via its negative action on the production of T cell attracting chemokines, and that its targeting improves the efficacy of anti-PD1 immunotherapy. Overall, the major role of ZEB1 in preventing T cell infiltration suggests it may constitute a new target in metastatic melanoma.
2022-03-23 | GSE169203 | GEO