Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NFE2L2 mutations enhance radioresistance in head and neck cancer by modulating intratumoral myeloid cells

ABSTRACT: NFE2L2 mutations enhance radioresistance in head and neck cancer by modulating intratumoral myeloid cells

PROVIDER: PRJNA922975 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23051063_1.fastq.gz	Fastqsanger.gz
	SRR23051063_2.fastq.gz	Fastqsanger.gz
	SRR23051064_1.fastq.gz	Fastqsanger.gz
	SRR23051064_2.fastq.gz	Fastqsanger.gz
	SRR23051065_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 48

Similar Datasets

NFE2L2 Mutations Enhance Radioresistance in Head and Neck Cancer by Modulating Intratumoral Myeloid Cells.

Project description:Radiotherapy (RT) is one of the primary treatments of head and neck squamous cell carcinoma (HNSCC), which has a high-risk of locoregional failure (LRF). Presently, there is no reliable predictive biomarker of radioresistance in HNSCC. Here, we found that mutations in NFE2L2, which encodes Nrf2, are associated with a significantly higher rate of LRF in patients with oral cavity cancer treated with surgery and adjuvant (chemo)radiotherapy but not in those treated with surgery alone. Somatic mutation of NFE2L2 led to Nrf2 activation and radioresistance in HNSCC cells. Tumors harboring mutant Nrf2E79Q were substantially more radioresistant than tumors with wild-type Nrf2 in immunocompetent mice, whereas the difference was diminished in immunocompromised mice. Nrf2E79Q enhanced radioresistance through increased recruitment of intratumoral polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and reduction of M1-polarized macrophages. Treatment with the glutaminase inhibitor CB-839 overcame the radioresistance induced by Nrf2E79Q or Nrf2E79K. RT increased expression of PMN-MDSC-attracting chemokines, including CXCL1, CXLC3, and CSF3, in Nrf2E79Q-expressing tumors via the TLR4, which could be reversed by CB-839. This study provides insights into the impact of NFE2L2 mutations on radioresistance and suggests that CB-839 can increase radiosensitivity by switching intratumoral myeloid cells to an antitumor phenotype, supporting clinical testing of CB-839 with RT in HNSCC with NFE2L2 mutations.SignificanceNFE2L2 mutations are predictive biomarkers of radioresistance in head and neck cancer and confer sensitivity to glutaminase inhibitors to overcome radioresistance.

| S-EPMC10023320 | biostudies-literature

NFE2L2 mutations enhance radioresistance in head and neck cancer by modulating intratumoral myeloid cells

Project description:To identify the mechanism by which Nrf2E79Q mediates RT resistance and CB-839 overcomes RT resistance in Nrf2E79Q, we performed RNA sequencing of SAS cells stably expressing either Nrf2WT or Nrf2E79Q treated with RT±CB-839 and analyze the differentially expressed genes in Nrf2E79Q vs. Nrf2WT cells.

2023-03-10 | GSE222658 | GEO

FN1 expression is a marker of radioresistance in head and neck squamous cell carcinoma

2011-06-09 | GSE21644 | GEO

FN1 expression is a marker of radioresistance in head and neck squamous cell carcinoma

Project description:The goal of this project was to analyze differential expression in head and neck cancer cells with various intrinsic radiosensitivity. The gene expression profiles of the cell lines were determined using the Human Genome U133 plus 2.0 Arrays (Affymetrix, Santa Clara, CA). The UTSCC cells were cultured in DMEM (Gibco) supplemented with 2mM glutamine, 1% non-essential amino acids, 100 IU/ml penicillin-G, 50ug/ml streptomycin, and 5% fetal bovine serum (all from Gibco, Paisley, UK). Total RNA was prepared from 3 x 10^6 cells using the RNeasy Mini Protocol (Qiagen GmbH, Hilden, Germany). The study included a total of 10 samples with 2 seperate experiments from 5 cell lines respectivley.

2011-06-09 | E-GEOD-21644 | biostudies-arrayexpress

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

Mevalonate pathway activity is a key determinant of radiation sensitivity in head and neck cancer

Project description:Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here we report a novel role for statin-based treatment of HNSCCs as an actionable and safe adjuvant to radiotherapy. Proteomic profiling and comparison of radiosensitive and radioresistant HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway. Consistent with this finding, inhibition of the mevalonate pathway by pitavastatin (and other related statins) sensitized SQ20B cells to ionizing radiation (IR) and reduced their clonogenic potential. In an effort to uncover the mechanism behind this statin-mediated sensitization, we analyzed prenylation of several important cellular targets upon combined IR-statin treatment. Overall, this study reinforces the view that the mevalonate pathway is a promsing novel therapeutic target in radioresistant HSNCCs.

2019-06-25 | PXD007188 | Pride

Head and neck squamous cell carcinoma

Project description:Quantitative (iTRAQ 4-plex) proteomic analysis of progressive head and neck cancers

2022-03-01 | PXD001438 | Pride

Transcriptomic profiling of murine Nfe2l2 knockout melanoma cells

Project description:The role of Nfe2l2 in established murine melanoma cells was studied by analyzing expression profiles of control and Nfe2l2 knockout melanoma cells, generated by CRISPR/Cas9.

2020-10-01 | GSE141912 | GEO

Intratumoral Microbiome in Head and Neck Paragangliomas.

Project description:Head and neck paragangliomas (HNPGLs) are rare neoplasms arising from paraganglia of the parasympathetic nervous system. HNPGLs are characterized by high vascularity and are located in proximity to major vessels and nerves, which may be potential sources of microbial invasion in these tumors. There have been no studies in the literature on the microbiota in HNPGLs. Investigation of the microbiome associated with paragangliomas is important for understanding tumor pathogenesis. In this study, we investigated the microbiome composition in two sets of HNPGLs. First, 29 fresh frozen (FF) tissues were subjected to 16S rRNA gene sequencing; concurrently, a panel of candidate laboratory-derived contaminants was investigated. Second, we analyzed microbial reads from whole transcriptome sequencing data obtained for 82 formalin-fixed paraffin-embedded (FFPE) HNPGLs. The bacterial diversity in FF tumors was found to be significantly lower than that observed in FFPE HNPGLs. Based on 16S rRNA gene sequencing, only seven bacterial families were identified as potential tumor inhabitants: Bryobacteraceae, Enterococcaceae, Neisseriaceae, Legionellaceae, Vibrionaceae, Obscuribacteraceae, and Mycobacteriaceae. However, RNA-Seq demonstrated higher sensitivity for identifying microbiome composition and revealed abundant bacterial families that partially correlated with those previously described in pheochromocytomas and extra-adrenal paragangliomas. No viruses were found in HNPGLs. In summary, our findings indicated the presence of a microbiome in HNPGLs, comprising a number of bacterial families that overlap with those observed in pheochromocytomas/paragangliomas and glioblastomas.

| S-EPMC11394710 | biostudies-literature

Pretreatment microRNA expression impacting on epithelial to mesenchymal transition predicts intrinsic radiosensitivity in head and neck cancer cell lines and patients [FaDu]

Project description:Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex-vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biological processes that could be targeted to overcome intrinsic resistance. Experimental design: We analyzed both micro- and messenger RNA expression in a large panel of HNSCC cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of laryngeal cancer patients. Results: MiRs, mRNAs and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial to mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of laryngeal cancer patients. Conclusions: These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially miR-203, measured in pre-treatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors.

2016-03-19 | GSE79371 | GEO

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