NRF2 activation in TRP53:P16 deficient mice drives oral squamous cell carcinoma
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Eclipse
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: 
Nathan Wamsleyu
LAB HEAD: Ben Major
PROVIDER: PXD048887 | Pride | 2024-01-31
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| CHROMATOGRAMS.zip | Other | |||
| MA5253_A_M919h_MOUSESQ_112223.raw | Raw | |||
| MA5254_B_M919e_MOUSESQ_112223.raw | Raw | |||
| MA5255_C_857C1_MOUSESQ_112223.raw | Raw | |||
| MA5256_D_857C2_MOUSESQ_112223.raw | Raw |
Items per page: 5 1 - 5 of 28 |
Similar Datasets
Project description:The NFE2L2/NRF2 oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry (MS)-based targeted proteomics assay based on internal standard triggered parallel reaction monitoring (IS-PRM) to quantify 69 NRF2 pathway components and targets as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved the existing IS-PRM acquisition algorithm, called SureQuantTM, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded (FFPE) HNSCCs, NRF2 signaling intensity positively correlated with NRF2 activating mutations and with SOX2 protein expression. PD-L2/CD273 and protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus (HPV) infection status. p16/CDKN2A protein expression positively correlated with the HPV oncogenic E7 protein, and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or FFPE archived tissues in under 90 minutes.
2023-06-13 | PXD042949 | Pride
Project description:The NFE2L2/NRF2 oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry (MS)-based targeted proteomics assay based on internal standard triggered parallel reaction monitoring (IS-PRM) to quantify 69 NRF2 pathway components and targets as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved the existing IS-PRM acquisition algorithm, called SureQuantTM, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded (FFPE) HNSCCs, NRF2 signaling intensity positively correlated with NRF2 activating mutations and with SOX2 protein expression. PD-L2/CD273 and protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus (HPV) infection status. p16/CDKN2A protein expression positively correlated with the HPV oncogenic E7 protein, and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or FFPE archived tissues in under 90 minutes.
2023-06-08 | PXD041163 | Pride
Project description:The NFE2L2/NRF2 oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry (MS)-based targeted proteomics assay based on internal standard triggered parallel reaction monitoring (IS-PRM) to quantify 69 NRF2 pathway components and targets as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved the existing IS-PRM acquisition algorithm, called SureQuantTM, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded (FFPE) HNSCCs, NRF2 signaling intensity positively correlated with NRF2 activating mutations and with SOX2 protein expression. PD-L2/CD273 and protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus (HPV) infection status. p16/CDKN2A protein expression positively correlated with the HPV oncogenic E7 protein, and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or FFPE archived tissues in under 90 minutes.
2023-06-08 | PXD041162 | Pride
Project description:This is the proteomics part of the above project. Purpose: No blood-based biomarkers to detect OPSCC early before symptoms develop or before clinically visible. Diagnosis is solely based on histology of a visible tumour. Most OPSCC patients are diagnosed at an advanced stage, which leads to significant morbidity and poor survival. If high-risk patients were identified with blood-based biomarkers before clear clinical manifestations, tumours could be detected and treated at an earlier stage. Causes of OPSCC include smoking, alcohol misuse, and human papillomavirus (HPV). Tumours are separated according to WHO recommendations into HPV+ OPSCC and HPV- OPSCC using the proxy histological marker p16. We additionally separated our patients into these groups to determine whether the serum glycopeptides would differ between HPV+ and HPV- tumours, as these are distinct clinical entities. Patients and Methods: Pre-treatment sera from 74 patients with OPSCC (including 26 p16- tumours and 48 p16+ tumours) and 12 controls were used, collected between the years 2012 and 2015 at the Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland. Samples were grouped as follows: early stage p16+ OPSCC (stage I only), early stage p16- OPSCC (stage I-II), p16+ (any stage), p16- (any stage), controls. In-parallel quantitative bulk serum proteomics and serum glycopeptidomics were performed. Results: We identified 78 bulk proteins in the serum, of which 33 significantly differed between early-stage p16- OPSCC and controls, 22 between early-stage p16+ OPSCC and controls, 1 between early-stage p16+ and early-stage p16- OPSCCs, and 30 between all p16+ and p16- OPSCCs. We identified glycopeptides from proteins including but not limited to alpha-1-antitrypsin, haptoglobin, and Immunoglobulin heavy constant alpha 1, and compared these with the protein expression levels in each comparison. Conclusions: We have identified novel serum glycopeptide biomarkers detect early-stage OPSCCs, to be evaluated further as a diagnostic panel to detect preclinical OPSCC in at-risk patients.
2024-01-26 | PXD016727 | Pride
Project description:This is the glycopeptide part of the above project. Purpose: No blood-based biomarkers to detect OPSCC early before symptoms develop or before clinically visible. Diagnosis is solely based on histology of a visible tumour. Most OPSCC patients are diagnosed at an advanced stage, which leads to significant morbidity and poor survival. If high-risk patients were identified with blood-based biomarkers before clear clinical manifestations, tumours could be detected and treated at an earlier stage. Causes of OPSCC include smoking, alcohol misuse, and human papillomavirus (HPV). Tumours are separated according to WHO recommendations into HPV+ OPSCC and HPV- OPSCC using the proxy histological marker p16. We additionally separated our patients into these groups to determine whether the serum glycopeptides would differ between HPV+ and HPV- tumours, as these are distinct clinical entities. Patients and Methods: Pre-treatment sera from 74 patients with OPSCC (including 26 p16- tumours and 48 p16+ tumours) and 12 controls were used, collected between the years 2012 and 2015 at the Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland. Samples were grouped as follows: early stage p16+ OPSCC (stage I only), early stage p16- OPSCC (stage I-II), p16+ (any stage), p16- (any stage), controls. In-parallel quantitative bulk serum proteomics and serum glycopeptidomics were performed. Results: We identified 78 bulk proteins in the serum, of which 33 significantly differed between early-stage p16- OPSCC and controls, 22 between early-stage p16+ OPSCC and controls, 1 between early-stage p16+ and early-stage p16- OPSCCs, and 30 between all p16+ and p16- OPSCCs. We identified glycopeptides from proteins including but not limited to alpha-1-antitrypsin, haptoglobin, and Immunoglobulin heavy constant alpha 1, and compared these with the protein expression levels in each comparison. Conclusions: We have identified novel serum glycopeptide biomarkers detect early-stage OPSCCs, to be evaluated further as a diagnostic panel to detect preclinical OPSCC in at-risk patients.
2024-01-26 | PXD016709 | Pride
Project description:Genome wide DNA methylation profiling of normal and primary oropharyngeal squamous cell carcinoma tissue samples, some infected with the human papilloma virus (HPV). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 27,000 CpGs in tissue samples. Samples included 46 oropharyngeal SCC primary tumors and 46 normal adjacent mucosal samples. For each tumor sample, HPV status (positivity based on both DNA and E6/E7 RNA) and p16 immunohistochemistry status is included. Bisulphite converted DNA from the 46 primary tumors and 46 matched adjacent normal samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
2014-06-07 | E-GEOD-58272 | biostudies-arrayexpress
Project description:Increased incidence of oropharyngeal squamous cell carcinoma (OPSCC) is mainly related to Human Papilloma Virus (HPV) infection. As OPSCCs are often diagnosed at an advanced stage, mortality and morbidity remain high. There are no diagnostic biomarkers for early stage detection of OPSCC. Serum from 25 patients with stage I-II OPSCC and 12 disease- individuals were studied with quantitative label-free proteomics using ultra-definition MSE. Statistical analyses were performed to identify proteins most reliably distinguishing early stage OPSCCs from controls. P16 was used as a surrogate marker for HPV. P16-positive and -negative tumours were also analysed separately. With two or more unique proteins per identification, 176 proteins were quantified. A clear separation between patients with early-stage tumours and controls was seen in principal component analysis. Latent structures discriminant analysis identified 96 proteins most reliably differentiating OPSCC patients from controls, with 13 upregulated and 83 downregulated in study cases. The set of proteins was studied further with network, pathway and protein-protein interaction analyses, and found to participate in e.g. lipid metabolism. We identified patients with early stage OPSCC from controls based on their serum proteome, and suggest a protein set for further evaluation as a diagnostic biomarker panel for OPSCC.
2018-07-11 | PXD008445 | Pride
Project description:Genome wide DNA methylation profiling of normal and primary oropharyngeal squamous cell carcinoma tissue samples, some infected with the human papilloma virus (HPV). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 27,000 CpGs in tissue samples. Samples included 46 oropharyngeal SCC primary tumors and 46 normal adjacent mucosal samples. For each tumor sample, HPV status (positivity based on both DNA and E6/E7 RNA) and p16 immunohistochemistry status is included.
2014-06-07 | GSE58272 | GEO
Project description:This experiment combines four RNA-Seq datasets of soybean seeds at the following developmental stages: 1) seed globular stage, E-GEOD-57349 (https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-57349/); 2) seed heart stage, E-GEOD-57350 (https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-57350/); 3) seed cotyledon stage, E-GEOD-57606 (https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-57606/) and 4) seed early maturation stage, E-GEOD-46096 (https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-46096/). Authors investigated soybean seed development because (1) soybean seeds are a major source of food and fuel, (2) soybean seeds have been an excellent system for studying the basic processes controlling seed development for over three decades, and (3) new soybean genomic resources, including the sequence of the soybean genome and the gene expression profiles for all seed compartments, tissues, and cell types, can be used to gain new insights into the regulatory processes required for seed differentiation. Authors sequenced messenger RNA populations of specific soybean seed compartments to provide new insights into gene expression that are important for âmaking a soybean seed.â
2014-05-07 | E-MTAB-4045 | biostudies-arrayexpress
Project description:To investigate effects of long-term intake of RPS on gene expression in the colon and liver of pigs,thirty-six Duroc × Landrace × Large White growing barrows were randomly allocated to corn starch (CS) and RPS groups. Each group consisted of six replicates (pens), with three pigs per pen. Pigs in the CS group were offered a corn/soybean-based diet, while pigs in the RPS group were put on a diet in which 230 g/kg (growing period) or 280 g/kg (finishing period) purified corn starch was replaced with purified RPS during a 100-day trial. Liver transcriptomic results showed that the expression of CD36, CPT1B and ACADM was down-regulated, while AGPAT4, GPAT, FABP1 and FABP3 were up-regulated by the RPS diet, indicating a decrease in fatty acid intake and synthesis, and an increase in fatty acid oxidation and glycerophospholipid synthesis.Analysis of the colonic transcriptome profiles revealed that the RPS diet changed the colonic expression profile of the host genes mainly involved in immune response pathways. RPS significantly increased proinflammartory cytokine IL-1? gene expression and suppressed genes involved in lysosome. Thirty-six Duroc × Landrace × Large White growing barrows (70 days of age, 23.78 ± 1.87 kg) were randomly allocated to two groups, each group consisting of three pigs per pen, and six replicates. Pigs in the control group were offered a corn/soybean-based diet, while 230 g/kg purified corn starch (CS) was replaced with purified RPS in the RPS diet group. Diets were formulated according to the nutrient requirements of the National Research Council (1998). When animals reached the age of 120 days, diets were adapted to the nutrient requirements of the animals (finishing diet) and the amount of purified starch increased to 280 g of CS or RPS per kilogram of feed. Pigs had unlimited access to feed and water throughout the experimental period, which consisted of two 50-day trials in which the pigs consumed the growing diet (days 0-50) and finishing diet (days 51-100), respectively. On day 100, one pig from each replicate that met the target slaughter weight (105 to 110 kg) was slaughtered. The liver and colonic mucosa tissues were collected and preserved in liquid nitrogen for gene expression analysis.
2015-07-25 | E-GEOD-71305 | biostudies-arrayexpress