Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15321300.fastq.gz | Fastqsanger.gz | |||
| SRR15321301_1.fastq.gz | Fastqsanger.gz | |||
| SRR15321301_2.fastq.gz | Fastqsanger.gz | |||
| SRR15321302_1.fastq.gz | Fastqsanger.gz | |||
| SRR15321302_2.fastq.gz | Fastqsanger.gz |
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Project description:Melanoma brain metastasis (MBM) response to treatment varies greatly among patients, affecting overall prognosis and survival. This study aims to provide a comprehensive multi-omics overview of MBM by investigating tumor tissue composition at spatial, proteomic and transcriptomic levels, elucidating the spatial tumor landscape, characterizing tumor tissue cell populations and identifying enriched signaling pathways in the MBM tumor tissue. We found higher inter-tumoral heterogeneity than intra-tumoral heterogeneity in MBM at the protein and transcriptional levels. The treatment-naive patient exhibited high intra-tumoral heterogeneity (ITH) compared to patient who received treatment, with ITH levels varying across neighboring regions in all patient tumors. Significant global protein and cell type enrichment associated with malignant cells, macrophages, CAFs, and immune cells was observed in MBM using cellular deconvolution and tumor microenvironment (TME) analysis. The presence of MBM cell-type specific gene signatures, and enriched pathways identified using ST and bulk-seq provide an essential framework for understanding tumor composition and potential treatment-related effects in each MBM patient tumor. Taken together, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM, potentially guiding personalized treatment strategies in MBM therapy.
2025-07-17 | GSE275731 | GEO
Project description:Brain metastases (BrMs) are a devastating complication of solid tumors with challenging clinical management. In this study, immunogenomic and digital spatial analyses were applied to interrogate the peripheral blood and tumor specimens derived from 53 unique patients with metastatic brain tumors originating from different solid tumors including melanoma, breast cancer, lung cancer and renal cell carcinoma. In the peripheral blood, lower levels of neutrophil -lymphocytes ratio (NLR) were detected at time of craniotomy in patients with melanoma-derived brain metastasis (MBM) vs. non-melanoma- derived brain metastasis (non-MBM). Independently from the primary tumor of derivation, patients with BrMs and increased NLR levels were characterized by shorter overall survival (OS) following craniotomy. In the tumor microenvironment (TME), molecular evaluations performed on FFPEs revealed higher expression of genes and mRNA signatures identifying NK cells, CD8 cells and B cells in MBM (n=13) vs. non-MBM brain metastasis (n=41). Focusing on CD8 cells, higher infiltration of CD8+ cells were observed in patients with MBM with longer OS following craniotomy. Spatial proteomic analysis further highlighted the infiltration of CD8+ cells, antigen presenting cells- (HLA-DR+, CD11c+, B2M+), agonists of T cell activity (CD137+, CD40+) and B cells (CD20+) enriched in MBM vs non-MBM. On the contrary, an increased expression of genes associated with neuro-development, cell- cell adhesion, neutrophil enrichment together with the increased infiltrations of cells promoting neuro-differentiation (Neun+, S100+), immune regulatory functions (CD25+, CD127+), and granulocytes aggregation (CD66b+) were observed in non-MBM vs. MBM. These findings highlight that the TME of BrMs plays a pivotal role in the pathogenesis and therapeutic resistance of BrMs derived from different solid tumors. Our results also suggest that distinct neuro-immune interplay may contribute to treatment resistance in BrMs.
2024-09-11 | GSE245467 | GEO
Project description:Bulk ATAC-seq on 24 patient-derived cell lines corresponding to 4 melanoma brain metastases (MBM) and 4 peripheral/extracranial melanoma metastses (ECM).
2022-07-06 | GSE205033 | GEO
Project description:We performed single-cell/nuclei RNA-sequencing (sc/snRNA-seq) of 22 treatment-naïve melanoma brain metastases (MBM; 5 samples using scRNA-seq and 17 snRNA-seq) from 21 patients and 10 treatment-naïve extracranial (peripheral) metastases (MPM; all snRNA-seq) from 10 patients . In total, we recovered 145,555 cell transcriptomes in 32 samples including 73,369 cells from MBM and 72,186 from MPM.
2022-07-06 | GSE200218 | GEO
Project description:Our study provides a comprehensive multiomics overview of each patient’s tumor, revealing tumor cell types, proteomics, and transcriptomic changes related to melanoma brain metastasis (MBM). Here, we have applied the HiRIEF pre-fractionation and tandem mass tags (TMT)-16plex based peptide quantification to generate proteomes of multiple neighboring regions within each MBM tumor tissue. PCA and Hierarchical clustering analysis illustrated higher inter-tumoral heterogeneity than intra-tumoral heterogeneity of MBM at the protein levels, as lesions from the same patients are grouped into a single cluster. The treatment-naive patient (P3) exhibited high intra-tumoral heterogeneity (ITH) compared to treated ones, with ITH levels varying across neighboring regions in patient tumors. Differential expression analysis highlighted enriched protein and gene clusters for all patient comparisons, including innate immune proteins, macrophage activation, T- and B-cell signaling, and key cancer pathways (e.g., epithelial-mesenchymal transition, cell adhesion, notch signaling, oxidative phosphorylation and cell cycle checkpoints). Genes involved in functional processes characteristic of MBM cell types, tumor-immune interactions, and signaling mechanisms were more highly correlated with their protein levels. Overall, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM.
2025-07-21 | PXD055089 | Pride
Project description:Our study provides a comprehensive multiomics overview of each patient’s tumor, revealing tumor cell types, proteomics, and transcriptomic changes related to melanoma brain metastasis (MBM). Here, we have applied the HiRIEF pre-fractionation and tandem mass tags (TMT)-16plex based peptide quantification to generate proteomes of multiple neighboring regions within each MBM tumor tissue. PCA and Hierarchical clustering analysis illustrated higher inter-tumoral heterogeneity than intra-tumoral heterogeneity of MBM at the protein levels, as lesions from the same patients are grouped into a single cluster. The treatment-naive patient (P3) exhibited high intra-tumoral heterogeneity (ITH) compared to treated ones, with ITH levels varying across neighboring regions in patient tumors. Differential expression analysis highlighted enriched protein and gene clusters for all patient comparisons, including innate immune proteins, macrophage activation, T- and B-cell signaling, and key cancer pathways (e.g., epithelial-mesenchymal transition, cell adhesion, notch signaling, oxidative phosphorylation and cell cycle checkpoints). Genes involved in functional processes characteristic of MBM cell types, tumor-immune interactions, and signaling mechanisms were more highly correlated with their protein levels. Overall, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM.
2025-07-21 | PXD055170 | Pride
Project description:Our study provides a comprehensive multiomics overview of each patient’s tumor, revealing tumor cell types, proteomics, and transcriptomic changes related to melanoma brain metastasis (MBM). Here, we have applied the HiRIEF pre-fractionation and tandem mass tags (TMT)-16plex based peptide quantification to generate proteomes of multiple neighboring regions within each MBM tumor tissue. PCA and Hierarchical clustering analysis illustrated higher inter-tumoral heterogeneity than intra-tumoral heterogeneity of MBM at the protein levels, as lesions from the same patients are grouped into a single cluster. The treatment-naive patient (P3) exhibited high intra-tumoral heterogeneity (ITH) compared to treated ones, with ITH levels varying across neighboring regions in patient tumors. Differential expression analysis highlighted enriched protein and gene clusters for all patient comparisons, including innate immune proteins, macrophage activation, T- and B-cell signaling, and key cancer pathways (e.g., epithelial-mesenchymal transition, cell adhesion, notch signaling, oxidative phosphorylation and cell cycle checkpoints). Genes involved in functional processes characteristic of MBM cell types, tumor-immune interactions, and signaling mechanisms were more highly correlated with their protein levels. Overall, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM.
2025-07-21 | PXD055172 | Pride
Project description:Melanoma brain metastasis (MBM) is linked to dismal prognosis, low overall survival, and is detected in up to 80% of patients at autopsy. Circulating tumor cells (CTCs) are the smallest functional units of cancer and precursors of fatal metastasis. We previously employed an unbiased multilevel approach to discover a unique ribosomal protein large/small subunits (RPL/RPS) CTC gene signature associated with MBM. Here, we hypothesized that CTC-driven MBM secondary metastasis (?metastasis of metastasis? per clinical scenarios), has targeted organ specificity for liver. We injected parallel cohorts of immunodeficient and newly-developed humanized NBSGW (HuNBSGW) mice with cells from CTC-derived MBM to identify secondary metastatic patterns. We found the presence of a melanoma brain-liver metastasis axis in humanized NBSGW mice. Further, RNA-Seq analyses of tissues showed a significant upregulation of the RPL/RPS CTC gene signature linked to metastatic spread to liver. Additional RNA-Seq of CTCs from HuNBSGW blood revealed extensive CTC clustering with human B cells in these mice. CTC:B cell clusters were also upregulated in blood of primary melanoma patients, and maintained either in CTC-driven MBM or MBM CTC-derived cells promoting liver metastasis. CTC-generated tumor tissues were interrogated at single-cell gene and protein expression levels (10x Genomics Xenium and HALO spatial biology platforms, respectively). Collectively, our findings suggest that heterotypic CTC:B cell interactions can be critical at multiple stages of metastasis. This study provides important insights for relevance of pro-metastatic CTC:B cell clusters extending from primary metastatic disease, and identifies new targets for therapies of clinical metastasis to improve patient care.
2025-01-14 | GSE280739 | GEO
Project description:We performed matched TCR-seq and single-cell RNA-sequencing of 5 treatment-naïve melanoma brain metastases (MBM) from 5 individual patients.
2022-07-06 | GSE200215 | GEO
Project description:Bulk RNA-seq on 24 patient-derived cell lines corresponding to 4 melanoma brain metastases (MBM) and 4 peripheral/extracranial melanoma metastses (ECM).
2022-07-06 | GSE200217 | GEO