Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparative skin cancer atlas and interactome: A multi-modal spatial approach to uncovering the cells and interactions underlying skin cancer diversity

ABSTRACT: The three major skin cancer types - squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma - account for >70% of all cancer. Although these cancers all derive from the outer skin layer (epidermis), variability in cell type composition and interactions causes substantial cross-cancer differences in disease initiation and invasive and metastatic potential. A knowledgebase of cell type composition and cell-to-cell interactions within the three skin cancers is needed to aid the assessment of risks and prognosis upon patient presentation. Here we integrated six distinct yet complementary spatial single-cell technologies to build the largest cell atlas and interactome of SCC, BCC, and melanoma to date. First, we performed single-cell RNA sequencing (scRNAseq) on >50,000 cells from 11 paired healthy and SCC patient biopsies. GeoMx spatial proteomics data independently validated the presence of rare immune cell types defined by scRNAseq. Visium and CosMx transcriptomic analyses were performed for all three skin cancer types to map spatial neighbourhoods and construct a cell-to-cell interaction atlas. We independently validated two key LR interactions, PD1_PDL1 and IL34_CSF1R, using Opal Multiplex Polaris and RNAscope data. Downstream analysis of IL34_CSF1R signalling zones suggested enrichment of IL34-related antigen presenting pathways in melanoma. Overall, we present a valuable database and analysis approaches to reveal potential biomarkers of initiation and progression of the most lethal type (melanoma) and the most common types (SCC and BCC) of skin cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221390 | GEO | 2022/12/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Molecular classification of non-melanoma skin cancer by gene expression profiling

Project description:Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype. The analysis of gene expression profiling among non-melanoma skin cancer types

2014-12-13 | E-GEOD-53462 | biostudies-arrayexpress

A robust experimental and computational framework analysis at multiple resolutions, modalities and coverages

Project description:We assessed the utilities of integrating four advanced sequencing and multiplex imaging technologies to study cancer-immune cell interactions. These four technologies include single-cell RNA sequencing and Spatial Transcriptomic (both measuring over >20,000 genes), RNA In Situ Hybridization (multiplex 4-12 genes) and Opal multiplex protein staining (4-9 proteins). We evaluated the approach to discover and validate cell-cell interaction in situ through in-depth analysis of two types of cancer, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which account for over 70% of skin cancer cases.

2022-07-26 | E-MTAB-11932 | biostudies-arrayexpress

Molecular classification of non-melanoma skin cancer by gene expression profiling

2014-12-13 | GSE53462 | GEO

Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma - Spatial Transcriptomics - 10X Visium

Project description:Our understanding of how human skin cells differ according to body site and tumour formation is limited. To address this we have created a multi-scale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single cell RNA sequencing, spatial global transcriptional profiling and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retain signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling during cancer neovascularization. Our findings suggest that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community.

2023-12-22 | E-MTAB-13084 | biostudies-arrayexpress

Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma - Spatial Transcriptomics - 10X Visium

Project description:Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this we have created a multi-scale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single cell RNA sequencing, spatial global transcriptional profiling and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community.

2023-12-22 | E-MTAB-13085 | biostudies-arrayexpress

Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation [RNA-seq]

Project description:The age-associated increase of cancer risk has been linked with stromal fibroblast senescence and early steps of Cancer Associated Fibroblast (CAF) activation. Surprisingly little is known about the role of androgen receptor (AR) signalling in this context. We show that AR expression is down-modulated in stromal fibroblasts underlying premalignant skin cancer lesions (actinic keratoses, AK) as well as in CAFs from the three major skin cancer types, squamous (SCC) and basal cell (BCC) carcinomas and melanomas. Decreased AR expression is linked to the concomitant down-modulation of CSL, key effector of canonical Notch signalling and global modulator of chromatin configuration, and it can be counteracted by treatment with BET inhibitors, which reverse CAF activation. Functionally, AR gene silencing in dermal fibroblasts results in p53-dependent senescence and induction of key CAF-effector genes, with AR physically converging with CSL in negative control of these genes. The findings are of functional significance as, in an orthotopic model of skin cancer, dermal fibroblasts with AR loss enhance significantly tumorigenicity of SCC and melanoma cells. As such, the findings establish AR as a novel potential target for stroma-focused cancer prevention and treatment.

2018-08-28 | GSE107319 | GEO

Androgen receptor functions as transcriptional repressor of Cancer Associated Fibroblast (CAF) activation [ChIP-seq]

2018-08-28 | GSE107320 | GEO

Novel Molecular Markers for non-melanoma skin cancer

Project description:normal skin (no), actinic keratosis (ak), and squamous cell carcinoma (scc) of the skin were examined: Carcinogenesis is a multi-step process indicated by several genes up- or down-regulated during tumor progression. The type and number of genes involved in non-melanoma skin cancer (NMSC) are still unclear. This study examined and identified different expressed genes in NMSC. Fifteen snap-frozen biopsies of five immunosuppressed organ-transplanted recipients each normal skin, actinic keratosis (AK) and invasive squamous cell carcinoma (SCC) were analysed. Total RNA was extracted reverse transcribed and biotin-labeled cRNA was used for hybridization with Affymetrix HG-U133A gene expression cDNA-microarrays containing 22,283 known genes. Confocal scanner evaluated the signals twice and data analysis was performed by predicition analysis of microarrays (PAM) using nearest shrunken centroids with the threshold 3.5 to identify genes best characterizing normal skin and skin cancer. ANOVA analysis was performed as a second independent method to identify differentially expressed genes (p<0.05, and p<0.15). Quantitative verification of 13 up- or down-regulated genes was performed by real-time RT-PCR and genes were confirmed by sequencing. Broad coherent patterns in normal skin vs. AK and SCC were observed for 118 genes. Some of the genes (e.g. annexin, lamin, and metalloproteinases) up-regulated in carcinomas in our study have previously reported as over-expressed in NMSC. In total 42 genes were up-regulated and 76 genes were down-regulated in non-melanoma skin cancer. The majority of genes identified have not been previously reported different expressed during non-melanoma skin carcinogenesis. Keywords: ordered

2006-06-30 | GSE2503 | GEO

Microarray analysis shows multiple signaling pathways are involved in basal cell carcinoma growth

Project description:BACKGROUND: Basal cell carcinoma (BCC) is the most common form of human cancer. Though the genetic mutation and subsequent aberrant signaling role of the Hedgehog pathway in BCC development is understood, little is known about the downstream genetic mechanisms underlying BCC growth. The characterization of molecular events would improve our understanding of carcinogenesis and may define new therapeutic intervention opportunities. OBJECTIVE: To identify differential gene expression associated with tumorigenesis promotion and to define common signaling pathways significant in BCC survival and growth. METHODS: Microarray analysis, using a 21K expanded sequence verified cDNA set was performed on tissues obtained from previously untreated patients undergoing Mohs surgical resection (8 superficial BCC, 8 nodular BCC, 7 morphea form, 8 normal skin). Significantly differentially expressed genes were identified by analysis of microarray results in various data sets and subsequently screened for signaling pathway involvement. Selected genes were validated using real-time PCR analysis using an expanded set of 31 BCC samples. RESULTS: The global gene expression profiles in BCCs and normal skin were distinguishable by unpaired T test. 2429 genes were at least 1.5 fold differentially expressed between BCC (all morphological types) and normal skin (p < 0.01). Multiple singaling pathways were activated, but the hedgehog, WNT, MAPK and calcium signal transduction pathways predominated. CONCLUSION: Our findings may have important implications for understanding the pathogenesis of BCC and suggest targeting of the WNT and MAPK pathways with therapeutic intervention. Keywords: disease state analysis

2006-12-15 | GSE6520 | GEO

Integrated multi-omics reveals the cellular and molecular interactions governing the invasive niche in skin cancer

Project description:To progress, tumors need to invade the surrounding tissues. However, the heterogeneity of cell types at the tumor-stroma interface and the complexity of their potential interactions hampered mechanistic insights for efficient therapeutic targeting. Here, combining single-cell and spatial transcriptomics on human basal cell carcinomas (BCCs), we define the cellular contributors of the invasive front. In the invasive niche, tumor cells harbor a collective migration phenotype, supported by the expression of cell-cell junction complexes. In physical proximity, we identify cancer-associated fibroblasts (CAFs) with extracellular matrix-remodeling features, as required to support collective migration. Moreover, while tumor cells specifically express Activin A, we find Activin A-induced gene signature enrichment in adjacent CAFs subpopulations, further supporting their biological crosstalk. Altogether, our data identify the subpopulations and their transcriptional reprogramming contributing to the spatial organization of the BCC invasive niche. They also bring the proof-of-concept for integrated spatial and single-cell multi-omics to decipher cancer-specific invasive properties and develop therapeutic targeting.

2022-06-29 | GSE181907 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data