Single-cell sequencing analysis reveals the tissue architecture and empowers clinical trial in advanced conjunctival melanoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA900194 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22254500_1.fastq.gz | Fastqsanger.gz | |||
| SRR22254500_2.fastq.gz | Fastqsanger.gz | |||
| SRR22254501_1.fastq.gz | Fastqsanger.gz | |||
| SRR22254501_2.fastq.gz | Fastqsanger.gz | |||
| SRR22254502_1.fastq.gz | Fastqsanger.gz |
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Project description:Single-cell sequencing analysis empowers clinical decision
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Project description:Conjunctival melanoma (CoM) is a potentially devastating tumor that can lead to distant metastasis. Despite various therapeutic strategies for distant metastatic CoM, the clinical outcomes remain unfavorable. Herein, we performed single-cell RNA sequencing (scRNA-seq) of 47,017 cells obtained from normal conjunctival samples (n = 3) and conjunctival melanomas (n = 7). Notably, we noticed a higher abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME), correlated with enhanced angiogenic capacity and increased VEGFR expression in distal metastatic CoM. Additionally, we observed a significant decrease in the proportion of total CD8+ T cells and an increase in the proportion of naive CD8+ T cells, contributing to a relatively quiescent immunological environment in distal metastatic CoM. These findings were confirmed through the analyses of 70,303 single-cell transcriptomes of 7 individual CoM samples, as well as spatially resolved proteomes of an additional 10 samples of CoMs. Due to the increase of VEGFR-mediated angiogenesis and a less active T cell environment in distal metastatic CoMs, a clinical trial (ChiCTR2100045061) has been initiated to evaluate the efficacy of VEGFR blockade in combination with anti-PD1 therapy for patients with distant metastatic CoM, showing promising tumor-inhibitory effects. In conclusion, our study uncovered the landscape and heterogeneity of the TME during CoM tumorigenesis and progression, empowering clinical decisions in the management of distal metastatic CoM. To our knowledge, this is the initial exploration to translate scRNA-seq analysis to a clinical trial dealing with cancer, providing a novel concept by accommodating scRNA-seq data in cancer therapy.
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Project description:NanoString data on 12 conjunctival melanomas and mucosal melanoma The objective was to compare conjunctival melanoma with other mucosal melanomas at the RNA level using NanoString expression analysis of FFPE material.
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Project description:The underlying mechanisms of conjunctival fibrosis are complex and involve multiple factors and signaling pathway. Wnt/β-catenin signaling pathway plays an important role in organelle fibrosis. In this study, ICG-001 that inhibiting Wnt/β-catenin pathway has been applied in TGFβ1-induced fibrosis model of primary human conjunctival fibroblasts (HConFs). To verify the regulator of TGFβ1-induced conjunctival fibrosis, 4D DIA technology and proteomics analysis were used to identify the differentially expressed genes and the enrichment KEGG pathways.
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Project description:Trachoma is a poorly understood immuno-fibrogenic disease process, initiated by Chlamydia trachomatis (Ct). Differences in conjunctival gene expression profiles between Tanzanians with trachomatous conjunctival scarring (with (TSI) and without (TS) inflammation) and controls (C) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and Ct PCR. Transcriptome-wide microarray experiments were conducted on 41 samples (TSI 13, TS 15, C14). Cases had enrichment in proinflammatory cytokines and chemokines (IL1B, IL8, CXCL5, CCL20); Matrix metalloprotienases (MMP7, MMP9, MMP12); components of the cornified envelope / squamous metaplasia (SPRR2a, SPRR2F). Case - control study. Conjunctival swab samples were collected from people with trachomatious conjunctival scarring with (TSI) and without (TS) clinically visable inflammation compared to normal controls (C). Total RNA extracted and analysed on the Illumina WG-6 platrom. Additional extensive qRT-PCR work done on a large set of case-control pairs.
2011-07-31 | E-GEOD-24383 | biostudies-arrayexpress
Project description:Human conjunctival cell lines are useful tools for modeling ocular surface disease and evaluation of ocular drugs. Here we demonstrate that the IOBA-NHC and the ChWK conjunctival epithelial cell lines show, using an unbiased gene microarray approach, unique gene expression signatures that differ from primary conjunctival epithelial cells (PCEC) and conjunctival tissue. Globally, the expression profile obtained with the Affymetrix U133A chip (>22000 genes) from PCEC was clustered more closely to conjunctival tissue than either of the 2 cell lines. However, when restricted to Gene Ontology sub-categories: cellular defense, viral replication/cycling, antigen presentation, anti-oxidant pathways and ubiquitin ligase complex, the cell lines correlated reasonably well to PCEC (r > 0.70). In the category response to inflammation, correlation of cell lines to PCEC was poor (r = -0.012 and â0.041 for IOBA-NHC and ChWK respectively). In general, the expression profile in IOBA-NHC cells was better correlated to PCEC than the ChWK cells. This was statistically significant (p<0.05) when one considers all the genes on the chip, or for proteins in the extracellular region, response to wounding, stress, lipid, protein and organic acid metabolism, development and differentiation. Our results are useful for the choice of conjunctival cell lines, if necessary, in future experiments, to increase validity of extrapolation to clinical scenarios. Experiment Overall Design: Affymetrix U133A Genechip Experiment Overall Design: Experimental samples: Experiment Overall Design: IOBA-NHC cells (5 samples) Experiment Overall Design: Chang conjunctival epithelial cells WK derivative (4 samples) Experiment Overall Design: Primary conjunctival epithelial cells from explants (3 samples, obtained from cadaveric human explants) Experiment Overall Design: Conjunctival tissue from pterygium study where small piece uninvolved conjunctiva harvested (4 patients' RNA pooled to form one sample, total number of samples: 4) Experiment Overall Design: RT and hybridisation 16 hr according to Affymetrix protocol Experiment Overall Design: Labeling with biotin Experiment Overall Design: Washing microfluidics station 450 Experiment Overall Design: Analysis with Genespring GX 7.3.1 Experiment Overall Design: RMA normalisation following by normalisation to chip level median signal Experiment Overall Design: These processed data used for correlation analysis Experiment Overall Design: Further gene level normalisation to primary conjunctival epithelial cells samples for the purpose of fold change analysis to compare expression in IOBA or ChWK cells vs primary conjunctival epithelial cells.
2008-06-16 | E-GEOD-8633 | biostudies-arrayexpress
Project description:This study characterizes the transcriptional profile and the cellular tumor microenvironment of conjunctival lymphoma and identifies prognostically relevant biomarkers. 10 formalin-fixed and paraffin-embedded conjunctival lymphoma and 8 healthy conjunctival specimens were analyzed by MACE RNA sequencing. The 3,417 upregulated genes in conjunctival lymphoma were involved in processes such as B cell proliferation and Rac protein signaling, whereas the 1,188 downregulated genes contributed most significantly to oxidative phosphorylation and UV protection. The tumor microenvironment, as determined by deconvolution analysis, was mainly composed of multiple B cell subtypes which reflects the tumor’s B cell lineage. However, several T cell types, including T helper 2 cells and regulatory T cells, as well as innate immune cell types, such as anti-inflammatory macrophages and plasmacytoid dendrit-ic cells, were also strongly enriched in conjunctival lymphoma. A 13-biomarker prognostic panel, including S100A8 and S100A9, classified ocular and extraocular tumor recurrence, exceeded prognostic accuracy of Ann Arbor and AJCC staging, and demonstrated prognos-tic value for patient survival in 21 different cancer types in a database of 12,332 tumor pa-tients. These findings may lead to new options of targeted therapy and may improve prog-nostic prediction for conjunctival lymphoma.
2023-01-25 | GSE218618 | GEO
Project description:Trachoma is a poorly understood immuno-fibrogenic disease process, initiated by Chlamydia trachomatis (Ct). Differences in conjunctival gene expression profiles between Tanzanians with trachomatous conjunctival scarring (with (TSI) and without (TS) inflammation) and controls (C) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and Ct PCR. Transcriptome-wide microarray experiments were conducted on 41 samples (TSI 13, TS 15, C14). Cases had enrichment in proinflammatory cytokines and chemokines (IL1B, IL8, CXCL5, CCL20); Matrix metalloprotienases (MMP7, MMP9, MMP12); components of the cornified envelope / squamous metaplasia (SPRR2a, SPRR2F).
2011-08-01 | GSE24383 | GEO
Project description:Human conjunctival cell lines are useful tools for modeling ocular surface disease and evaluation of ocular drugs. Here we demonstrate that the IOBA-NHC and the ChWK conjunctival epithelial cell lines show, using an unbiased gene microarray approach, unique gene expression signatures that differ from primary conjunctival epithelial cells (PCEC) and conjunctival tissue. Globally, the expression profile obtained with the Affymetrix U133A chip (>22000 genes) from PCEC was clustered more closely to conjunctival tissue than either of the 2 cell lines. However, when restricted to Gene Ontology sub-categories: cellular defense, viral replication/cycling, antigen presentation, anti-oxidant pathways and ubiquitin ligase complex, the cell lines correlated reasonably well to PCEC (r > 0.70). In the category response to inflammation, correlation of cell lines to PCEC was poor (r = -0.012 and –0.041 for IOBA-NHC and ChWK respectively). In general, the expression profile in IOBA-NHC cells was better correlated to PCEC than the ChWK cells. This was statistically significant (p<0.05) when one considers all the genes on the chip, or for proteins in the extracellular region, response to wounding, stress, lipid, protein and organic acid metabolism, development and differentiation. Our results are useful for the choice of conjunctival cell lines, if necessary, in future experiments, to increase validity of extrapolation to clinical scenarios. Keywords: Cell type comparison
2007-08-03 | GSE8633 | GEO