Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell gene expression profile of patient-derived head and neck squamous carcinoma cells subjected to different treatments.

ABSTRACT: As other tumours, HNSCC are heterogenous, hence different cell populations within a given tumour may have different response towards treatment. Most of previous studies on HNSCC resistance towards treatment have been performed on “bulk” samples, which confound the influence of its heterogenous nature. In the recent years, single cell sequencing technologies have been developing rapidly and successfully applied to investigate numerous cancer response towards treatment. A recent scRNA-seq study on HNSCC cell lines confirmed the heterogenous response towards cetuximab. To further investigate both intrinsic and acquired resistance in HNSCC, we employed two primary cells modelling different responses towards selection with EGFR inhibitor, radiation, as well as a combination of EGFR inhibitor and radiation. These cell populations were studied using RAID technology, in which RNA and protein level were simultaneously quantified at a single cell resolution.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214146 | GEO | 2022/09/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression profile of patient-derived head and neck squamous carcinoma cells subjected to different treatments.

Project description:In order to investigate the mechanisms underlying response and resistance towards treatment in HNSCC, we used low passage in vitro HNSCC cultures from two patients, namely SJG26 and SJG17. Both cultures were subjected to selection by AG1478-mediated EGFR inhibition, radiation, as well as the combination of both for two weeks, generating presumably tolerant cell populations (AG, R and RAG). These tolerant cell populations and a non-treated population were subjected to bulk RNA-seq to study the overall gene expression profile of the cell populations.

2022-09-28 | GSE214145 | GEO

An Inducible TGF-Î²2-TGFÎ²R Pathway Modulates the Sensitivity of HNSCC Cells to Tyrosine Kinase Inhibitors Targeting Dominant Receptor Tyrosine Kinases

Project description:The epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of head and neck squamous cell carcinomas (HNSCC), and molecularly targeted therapy against the EGFR with the monoclonal antibody cetuximab modestly increases overall survival in head and neck cancer patients. We hypothesize that co-signaling through additional pathways limits the efficacy of cetuximab and EGFR-specific tyrosine kinase inhibitors (TKIs) in the clinical treatment of HNSCC. Analysis of gene expression changes in HNSCC cell lines treated 4 days with TKIs targeting EGFR and/or fibroblast growth factor receptors (FGFRs) identified transforming growth factor beta 2 (TGF-Î²2) induction in the three cell lines tested. Measurement of TGF-Î²2 mRNA validated this observation and extended it to additional cell lines. Moreover, TGF-Î²2 mRNA was increased in primary patient HNSCC xenografts treated for 4 weeks with cetuximab, demonstrating in vivo relevance of these findings. Functional genomics analyses with shRNA libraries identified TGF-Î²2 and TGF-Î² receptors (TGFÎ²Rs) as synthetic lethal genes in the context of TKI treatment. Further, direct RNAi-mediated silencing of TGF-Î²2 inhibited cell growth, both alone and in combination with TKIs. Also, a pharmacological TGFÎ²RI inhibitor similarly inhibited basal growth and enhanced TKI efficacy. In summary, the studies support a TGF-Î²2-TGFÎ²R pathway as a TKI-inducible growth pathway in HNSCC that limits efficacy of EGFR-specific inhibitors. HNSCC cell lines treated 4 days with TKIs targeting EGFR and/or fibroblast growth factor receptors (FGFRs) identified transforming growth factor beta 2 (TGF-Î²2) induction in the three cell lines tested

2016-03-22 | E-GEOD-67500 | biostudies-arrayexpress

FER kinase governs invasive tumor growth through dynamic control of oncogenic growth factor receptor activity

Project description:EGFR antagonism using monoclonal antibodies remains the only approved and targeted first line treatment option for non-resectable head and neck squamous cell carcinoma (HNSCC), yielding a modest 13% response rate. While it is clear that alternative growth factor receptor (GFR) signals govern refractory behavior towards EGFR antagonism, it remains unknown which upstream mechanisms control subcellular GFR activation. Here, we show that FER, a non-receptor tyrosine kinase, controls invasive tumor growth through dynamic GFR activation and recycling. Using patient derived organoid (PDO) models HNSCC we demonstrate that FER is essential for invasive growth in collagen extracellular matrix (ECM) networks. We show that inactivation of FER impairs growth factor dependent phosphorylation of EGFR-Y1068 and MET-Y1234/5. Additionally, FER controls ligand dependent endocytic recycling, and endocytic velocity, implying multifactorial functional regulation of proximal receptors during HNSCC invasion. Loss of function experiments using either genetic intervention or a FER PROteolysis-TArgeting Chimera (PROTAC) strategy in PDO-based xenograft mouse models, demonstrate that FER is essential for invasive growth and metastasis of HNSCC. Finally, we demonstrate direct clinical relevance by showing that FER expression levels correlate with poor survival in HNSCC patients. In sum, we conclude that FER is a master regulator of HNSCC invasive growth and metastasis, and nominate FER as a prominent candidate for targeted clinical intervention in HNSCC patients.

2024-03-31 | GSE255878 | GEO

Expression analysis of radio-resistant and -sensitive head and neck cancer cells

Project description:Head and Neck Squamous Cell Carcinoma (HNSCC) is a common cause of cancer death. Despite enormous technical advances in surgery and radiotherapy in the recent decade, survival of HNSCC patients has not markedly improved, with only 30% of patients diagnosed with advanced HNSCC that will survive for 5 years. This highlights the need to look into molecular processes leading to mechanisms of HNSCC radioresistance in HNSCC and identify novel radiosensitizers. To identify the lncRNAs associated with radiotherapy resistance in HNSCC, we performed RNA-seq analysis of radiation resistant and sensitive HNSCC cells.

2024-11-01 | GSE217645 | GEO

An Inducible TGF-β2-TGFβR Pathway Modulates the Sensitivity of HNSCC Cells to Tyrosine Kinase Inhibitors Targeting Dominant Receptor Tyrosine Kinases

Project description:The epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of head and neck squamous cell carcinomas (HNSCC), and molecularly targeted therapy against the EGFR with the monoclonal antibody cetuximab modestly increases overall survival in head and neck cancer patients. We hypothesize that co-signaling through additional pathways limits the efficacy of cetuximab and EGFR-specific tyrosine kinase inhibitors (TKIs) in the clinical treatment of HNSCC. Analysis of gene expression changes in HNSCC cell lines treated 4 days with TKIs targeting EGFR and/or fibroblast growth factor receptors (FGFRs) identified transforming growth factor beta 2 (TGF-β2) induction in the three cell lines tested. Measurement of TGF-β2 mRNA validated this observation and extended it to additional cell lines. Moreover, TGF-β2 mRNA was increased in primary patient HNSCC xenografts treated for 4 weeks with cetuximab, demonstrating in vivo relevance of these findings. Functional genomics analyses with shRNA libraries identified TGF-β2 and TGF-β receptors (TGFβRs) as synthetic lethal genes in the context of TKI treatment. Further, direct RNAi-mediated silencing of TGF-β2 inhibited cell growth, both alone and in combination with TKIs. Also, a pharmacological TGFβRI inhibitor similarly inhibited basal growth and enhanced TKI efficacy. In summary, the studies support a TGF-β2-TGFβR pathway as a TKI-inducible growth pathway in HNSCC that limits efficacy of EGFR-specific inhibitors.

2016-03-22 | GSE67500 | GEO

Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma

Project description:Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) remains one of the most difficult cancers to treat with limited chemotherapeutic options. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents; cetuximab, a monoclonal antibody (mAb) against Epidermal Growth Factor Receptor (EGFR), and AMG 479, a mAb against Insulin-like Growth Factor-1 Receptor (IGF-1R). In tumor tissue of this patient we observed gene expression modulation by cetuximab and AMG 479 suggesting crosstalk between the EGFR and IGF-1R pathways that may have sensitized the tumor to MTX. This represents a promising novel approach to development of targeted agents in refractory cancer. Keywords: tumor response 10 samples from different time points during course of treatment in a single individual.

2010-08-03 | E-GEOD-9600 | biostudies-arrayexpress

Evaluation of gene expression changes upon acquired resistance to anti-EGFR treatment in head and neck squamous cell carcinoma

Project description:We deciphered molecular mechanisms associated with acquired resistance to anti-EGFR targeted therapy in head and neck squamous cell carcinoma (HNSCC) by comparing gene expression profiles in cetuximab-sensitive and -resistant patient-derived xenograft (PDX) models of HNSCC. We generated and validated several HNSCC PDX models. Resistance mechanisms to anti-EGFR therapy were investigated in one of these PDX models (UCLHN04). First, sensitivity to cetuximab treatment was tested. This model showed high sensitivity to this drug. We induced acquired resistance to anti-EGFR therapy in this sensitive model by treating it chronically with anti-EGFR monoclonal antibody (cetuximab, 30 mg/kg/week) until resistance ensues. RNA-seq analysis was performed on samples coming from untreated and cetuximab-resistant PDX, revealing major changes of expression at the mRNA level.

2024-11-08 | GSE235417 | GEO

Genome-wide gene expression analysis of EGFR inhibitor erlotinib-resistant and -sensitive head and neck squamous cell carcinoma cell lines Cal-27, SCC-25, FaDu, and SQ20B

Project description:Despite the role of epidermal growth factor receptor (EGFR) signaling in head and neck squamous cell carcinoma (HNSCC) development and progression, clinical trials involving EGFR tyrosine kinase inhibitors (TKIs) have yielded poor results in HNSCC patients. Mechanisms of acquired resistance to the EGFR TKI erlotinib was investigated by developing erlotinib-resistant HNSCC cell lines (Cal-27, SCC-25, FaDu, and SQ20B) and comparing their gene expression profiles with their parental erlotinib-sensitive HNSCC cell lines using microarray analyses. Subsequent pathway and network analyses displayed a significant upregulation in immune response pathways. Role of immune/inflammatory signaling in acquired resistance to erlotinib in HNSCC was investigated.

2014-10-07 | GSE62061 | GEO

KIF2C is a critical regulator for malignant progression of head and neck squamous cell carcinoma

Project description:Head and neck squamous cell carcinoma(HNSCC) is a significant cause of mortality, while the underlying mechanism remains unclear. Recent studies indicate that KIF2C could play a vital role in tumor proliferation and metastasis. Our results demonstrate that KIF2C is highly expressed at both the mRNA and protein levels in HNSCC samples compared to normal samples. Gene ontol-ogy and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that differentially expressed genes were enriched in processes or pathways related to cell adhesion and cell mitosis in HNSCC. Additionally, a protein-protein interaction network was established, identifying KIF2C as a potential hub gene in HNSCC. Cell phenotype assays showed that KIF2C knockdown reduces cell migration and invasion ability and exhibited cell cycle arrest, high proportion of abnormal cell apoptosis and cell chromosome division mismatches in HNSCC cell line. RNA-seq and RT-PCR assay results revealed that KIF2C knockdown influenced the expression levels of PDGFA, CCNA1, RRM1, CCND2, CAV1, EGFR, SNAI2, KRT5, KRT14, NID1, TP63. TGFBR2, TGFB2, ICAM1, ITGB2, CDH2, CDH5, FN1. And KIF2C knockdown also decreased the phos-phorylation of mTOR, AKT, and ERK. Furthermore, in vivo studies have demonstrated that KIF2C knockdown significantly inhibits tumor proliferation in nude mice. As such, our study highlights the potential therapeutic role of KIF2C for HNSCC treatment.

2024-01-21 | GSE253500 | GEO

Integrative genomic analysis identifies clinically relevant subtypes of head and neck cancer characterized by hypoxia, T-cell infiltration, and EMT

Project description:Current classification of head and neck squamous cell carcinomas (HNSCC) based on anatomic site and clinical stage fails to capture biologic heterogeneity or adequately inform treatment. Here we use consensus clustering on 371 HNSCC in three cohorts, including a new cohort of 134 patients with locoregionally advanced HNSCC and 43% HPV(+) tumors to identify five HNSCC subtypes. Subtypes closely correlate with biologic processes (hypoxia, cytotoxic T-cell infiltration, copy number changes, EGFR/HER-ligand phenotype), survival, and HPV-status. Two biologically distinct HPV-associated subtypes are identified. Gene modules of candidate drivers characterize each subtype using the CONEXIC algorithm. The proposed 5-subtype classification provides a biologic basis for future clinical and preclinical studies and lays the groundwork for improved prognostication and therapy development in HNSCC. We use consensus clustering on 371 HNSCC in three cohorts, including a new cohort of 134 patients with locoregionally advanced HNSCC and 43% HPV(+) tumors to identify five HNSCC subtypes.

2015-03-04 | E-GEOD-40774 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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