Ontology highlight
ABSTRACT:
PROVIDER: PRJNA507919 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Exposure to electronic cigarette (e-cigarette) aerosol has been linked to a number of health concerns, including DNA damage, elevated oxidative stress, release of inflammatory cytokine, and dysfunctions in epithelial barriers. However, little is known about the effect of exclusive e-cigarette use on expression profiles of exosomal miRNAs, which play critical regulatory roles in many inflammatory responses and disease process including cancer. We aim to compare the exosomal microRNAs expression profile between exclusive e-cigarette users and normal controls without any tobacco product use (non-users). Using blood and urine samples from exclusive e-cigarette users and non-users in the Population Assessment of Tobacco and Health (PATH) Wave 1 study (2013-2014), we examined exosomal microRNAs expression levels through Illumina NextSeq 500/550 sequencing. We identified microRNAs that have significantly higher expression levels in exclusive e-cigarette users than non-users. Gene enrichment analysis of these significant exosomal microRNAs showed their involvement in cancer related pathways, which might indicate a potential elevated risk of cancer among exclusive e-cigarette users.
2024-07-10 | GSE253603 | GEO
Project description:Tobacco use is an independent adverse prognostic feature in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Despite this, the biologic features associated with tobacco use have not been systematically investigated in this population. We sought to characterize the genomic and immunologic features of HPV(+) OPSCC associated with tobacco use and adverse oncologic outcomes. Whole exome sequencing of 47 primary HPV(+) OPSCC tumors was performed to investigate mutational differences associated with tobacco exposure. To characterize the tumor immune microenvironment (TIME), targeted mRNA hybridization was performed. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at the time of diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T>C substitutions and a lower proportion of mutational signatures typically observed in HPV(+) OPSCC tumors, but was not associated with increases in mutational burden or the rate of recurrent oncogenic mutations. Our work suggests that rather than increased mutational burden, tobacco’s primary and clinically relevant association in HPV(+) OPSCC is immunosuppression of the tumor immune microenvironment.
2022-04-02 | GSE199029 | GEO
Project description:Molecular alterations induced by tobacco usage are not well characterized in oral squamous cell carcinoma. Tobacco consumption in chewing or smoking forms is a known risk factor in oral cancer. To understand proteomic changes due to tobacco usage in oral cancer patients we carried out comparative proteomic analysis in oral cancer patients who had history of tobacco using habits (patients who chewed tobacco and patients who smoked tobacco) and those with no history of tobacco consumption. Proteomic analysis resulted in the quantification of 5,848 proteins in smoker cohort, 5,216 in chewer, and 5,320 in non-user cohort. Among these 443, 72 and 139 were significantly dysregulated proteins (p-value≤ 0.05 and 2-fold change) in smoker, chewer and non-user cohorts, respectively. Gene ontology and pathway analysis of significantly dysregulated proteins revealed enrichment of distinct biological processes and pathways in each patient cohort. Proteins associated with collagen formation and antigen processing/presentation pathway were dysregulated in oral cancer patients who smoked tobacco, while keratinization process was enriched in patients who chewed tobacco. We also observed dysregulated proteins in non-users to be involved in ECM proteoglycans, metabolism of carbohydrates and glycosaminoglycans. Immune signaling pathways and muscle contraction were identified as common events dysregulated in all three cohorts. This study helps us to decipher the proteomic alterations induced by tobacco usage in oral cancer patients and will assist in identification of early detection markers to identify high risk population
2022-03-15 | PXD022808 | Pride
Project description:Accumulated genetic mutations or copy number alterations are frequently observed in esophageal squamous cell carcinoma (ESCC) patients. However, it is still elusive which gene is the driver to initiate ESCC. We identified key genetic determinants for ESCC development using CRISPR/Cas9-based multiple genes KO mouse esophageal organoid model. Trp53, Cdkn2a, and Notch1 triple KO (PCN) organoid showed the phenotypes of ESCC. These triple genes KO served for cell proliferation through building multiple root cell clusters and remodeling the immune landscape beneficial for tumorigenesis by Ccl2-Ccr2 mediated intercellular interactions. Ccl2-releasing PCN tumors were surrounded by exhausted T cells and M2 macrophages leading to immune evasion. The PCN-type tumor was observed in more than 30% of ESCC patients who express high levels of B2M, CCL2, and NF-kB. Our study unveiled genetic determinants for ESCC development crucial for cell-autonomous growth as well as non-cell autonomous interactions with immune cells.
2023-06-07 | GSE213904 | GEO
Project description:Accumulated genetic mutations or copy number alterations are frequently observed in esophageal squamous cell carcinoma (ESCC) patients. However, it is still elusive which gene is the driver to initiate ESCC. We identified key genetic determinants for ESCC development using CRISPR/Cas9-based multiple genes KO mouse esophageal organoid model. Trp53, Cdkn2a, and Notch1 triple KO (PCN) organoid showed the phenotypes of ESCC. These triple genes KO served for cell proliferation through building multiple root cell clusters and remodeling the immune landscape beneficial for tumorigenesis by Ccl2-Ccr2 mediated intercellular interactions. Ccl2-releasing PCN tumors were surrounded by exhausted T cells and M2 macrophages leading to immune evasion. The PCN-type tumor was observed in more than 30% of ESCC patients who express high levels of B2M, CCL2, and NF-kB. Our study unveiled genetic determinants for ESCC development crucial for cell-autonomous growth as well as non-cell autonomous interactions with immune cells.
2023-06-07 | GSE213927 | GEO
Project description:Tobacco in its smoke and smokeless form are major risk factors for ESCC (esophageal squamous cell carcinoma). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form. An understanding of molecular alterations associated with chewing tobacco exposure is vital for identifying molecular markers and potential targets. We developed an in-vitro cellular model by exposing non-transformed esophageal epithelial cells to chewing tobacco over eight month period. Chronic exposure to chewing tobacco led to increase in cell proliferation, invasive ability and anchorage independent growth indicating cell transformation. Molecular alterations associated with chewing tobacco exposure were characterized by carrying out exome sequencing and quantitative proteomic profiling of parental cells and chewing tobacco exposed cells. Quantitative proteomic analysis revealed that established cancer stem cell markers are elevated in tobacco treated cells. Decreased expression of enzymes associated with the glycolytic pathway and increased expression of a large number of mitochondrially localized proteins involved in the electron transport chain as well as enzymes of TCA cycle were also identified. Electron micrographs revealed increase in number and size of mitochondria. Based on these observations, we hypothesise that chronic treatment of esophageal epithelial cells with tobacco leads to a cancer stem cell-like phenotype. These cells also show characteristic OXPHOS phenotype which can be potentially targeted as a therapeutic strategy.
2019-11-11 | PXD013396 | Pride
Project description:Unlike smoking-related non-small cell lung cancers (NSCLC), oncogene-driven tumors are characterized by low mutational burdens and complex genomic landscapes. However, the clonal architecture and genomic landscape of the oncogene-driven tumors in smokers remains unknown. Here, we investigate the impact of tobacco smoking on the genomic and transcriptomic alterations in the context of oncogene-driven NSCLC.
| EGAS00001006942 | EGA
Project description:Characterization of the mutational landscape of the 5T murine models for multiple myeloma, by whole-exome sequencing.
2018-10-09 | E-MTAB-5282 | biostudies-arrayexpress
Project description:<p>International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not been identified by conventional epidemiology yet potentially make a substantial contribution to cancer burden1. This pertains to clear cell renal cell carcinoma (ccRCC), for which obesity, hypertension, and tobacco smoking are risk factors but do not explain its geographical variation in incidence2. Some carcinogens generate somatic mutations and a complementary strategy for detecting past exposures is to sequence the genomes of cancers from populations with different incidence rates and infer underlying causes from differences in patterns of somatic mutations. Here, we sequenced 962 ccRCC from 11 countries of varying incidence. Somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures likely caused by extracts of Aristolochia plants were present in most cases and rare elsewhere. In Japan, a mutational signature of unknown cause was found in >70% cases and <2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher kidney cancer incidence rates (p-value <6 × 10−18). Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension suggesting non-mutagenic mechanisms of action underlying these risk factors. The results indicate the existence of multiple, geographically variable, mutagenic exposures potentially affecting 10s of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>Geographic variation of mutagenic exposures in kidney cancer genomes – patient metadata files (<strong>Mutographs</strong>) associated with this study are available in the <strong>European Genome-Phenome Archive</strong>: https://ega-archive.org/datasets/EGAD00001012223.</p>
2024-03-26 | MTBLS9394 | MetaboLights