Differential proteome profile of tobacco abuser and oral cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Neel Sarovar Bhavesh
PROVIDER: PXD012295 | iProX | Thu Jan 10 00:00:00 GMT 2019
REPOSITORIES: iProX
Similar Datasets
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:Tobacco is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, the molecular mechanisms resulting in malignancy upon tobacco exposure are yet to be fully elucidated. We therefore sought to compare the molecular alterations in oral keratinocytes exposed to smoke and chewing tobacco. OKF6/TERT1 cells were exposed to cigarette smoke condensate or chewing tobacco for progressively increasing durations (2, 4, 6 and 8 months). We employed a TMT-based quantitative proteomics approach to investigate the adverse effects of chronic cigarette smoke or chewing tobacco exposure in oral keratinocytes. LC/MS3 analysis resulted in the quantification of 5,342 proteins and 2,821 proteins in cigarette smoke and chewing tobacco exposed cells, respectively. Upstream regulator analysis indicates the involvement of distinct regulators in CSC exposed cells compared to STE exposed cells. In addition, exome sequencing revealed discrete genetic alterations in cells exposed to each insult. Current analysis defines a clear distinction in the molecular dysregulation in oral cells in response to different tobacco-based insults. Some of the proteins dysregulated in cigarette smoke or chewing tobacco exposed cells may serve as potential early detection biomarkers which could aid in stratification of patients based on tobacco usage history.
2019-11-08 | PXD007127 | Pride
Project description:Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide including the Asian subcontinent. Oral carcinoma exhibits inherent heterogeneity in terms of the sites involved, etiology and pathology. They occur at multiple sites such as tongue, buccal mucosa, maxilla. Effective approaches towards improving survival rates in OSCC patients are primarily focused on early detection of the disease. The early clinical indication of the disease follows the development of potentially malignant lesions (leukoplakia/erythro-leukoplakia) with varied rates of transformation. Currently histopathological evaluation of oral biopsy is generally practiced to evaluate potential malignancy. However, human saliva has been considered to be a valuable medium for discovering biomarker molecules for malignancy. Exfoliated cancer cells may release protein or RNA molecules into the saliva or free molecules may be secreted or leaked from cancer cells representing gene expression changes associated with tumor development. Salivary proteins thus provide a strong option for development of non-invasive, point-of-care assays for screening/early detection of oral cancers. Dysplastic leukoplakia (LP) of the oral cavity is a potentially malignant condition for oral squamous cell carcinoma (OSCC), early detection of which is an unmet clinical need. In an effort to develop non-invasive biomarker based method for early detection of the disease, we have used quantitative mass spectrometry to identify differently abundant salivary proteins in OSCC (buccal mucosa) patients and individuals with potential to develop cancer (oral dysplastic leukoplakia) in comparison to healthy controls (with risk habits such as tobacco chewing or smoking).
2019-11-12 | PXD015722 | Pride
Project description:The practice of using chewing tobacco is common in certain socio-economic sections of southern Asia particularly in the Indian subcontinent. The molecular mechanism of smokeless tobacco which leads to malignancy is unclear. Chewing tobacco demonstrates a carcinogenic effect through chronic and not acute exposures. Using a cell line model, we studied the chronic effects of chewing tobacco on the proteome in normal oral keratinocytes (OKF6/TERT1). We carried out iTRAQ-based quantitative proteomic analysis of the untreated and chewing tobacco treated oral keratinocytes. LC-MS/MS analysis of this cell line pair resulted in the identification of 3,638 proteins of which 408 were found to be differentially expressed.
2016-12-14 | PXD001554 | Pride
Project description:Tobacco exposure has been established to be a major risk factor for developing oral squamous cell carcinoma (OSCC). The purpose of this study is to identify potential biomarkers to distinguish the biological effectsof combustible tobacco products from that of non-combustible tobacco products using normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines.
2017-06-23 | GSE89923 | GEO
Project description:For decades the tobacco plant has served as a model organism in plant biology to answer fundamental biological questions in the areas of plant development, physiology, and genetics. Due to the lack of sufficient coverage of genomic sequences, however, none of the expressed sequence tag (EST)-based chips developed to date cover gene expression from the whole genome. The availability of Tobacco Genome Initiative (TGI) sequences provides a useful resource to build a whole genome exon array, even if the assembled sequences are highly fragmented. Here, the design of a Tobacco Exon Array is reported and an application to improve the understanding of genes regulated by cadmium (Cd) in tobacco is described. From the analysis and annotation of the 1,271,256 Nicotiana tabacum fasta and quality files from methyl filtered genomic survey sequences (GSS) obtained from the TGI and ~56,000 ESTs available in public databases, an exon array with 272,342 probesets was designed (four probes per exon) and tested on two selected tobacco varieties. Two tobacco varieties out of 45 accumulating low and high cadmium in leaf were identified based on the GGE biplot analysis, which is analysis of the genotype main effect (G) plus analysis of the genotype by environment interaction (GE) of eight field trials (four fields over two years) showing reproducibility across the trials. The selected varieties were grown under greenhouse conditions in two different soils and subjected to exon array analyses using root and leaf tissue to understand the genetic make-up of the Cd accumulation. An Affymetrix Exon Array was developed to cover a large (~90%) proportion of the tobacco gene space. The Tobacco Exon Array will be available for research use through the Affymetrix array catalogue. As a proof of the exon array usability, we have demonstrated that the Tobacco Exon Array is a valuable tool for studying Cd accumulation in tobacco leaves. Data from field and greenhouse experiments supported by gene expression studies strongly suggested that the difference in leaf Cd accumulation between the two specific tobacco cultivars is dependent solely on genetic factors and genetic variability rather than on the environment.
2012-11-16 | GSE42319 | GEO
Project description:Purpose: we conducted a six time-point transcriptomic analysis using two tobacco cultivars with contrasting cold responses, Taiyan8 tobacco (TT, cold susceptibility) and Yanyan97 tobacco (YT, cold resistance). Methods: mRNA profiles of Tobacco seedlings from CK and cold-treated plants were generated by deep sequencing, in triplicate, usingIllumina Hiseq4500. The sequence reads that passed quality filters were analyzed at the transcript isoform level with methods: hisat2 (v2.0.5), SAMtools (v1.9). StringTie (v1.3.4d) and FeatureCounts (v1.6.4) Results: We found that both cultivars had common mechanisms to cope with cold stress, including common differentially expressed genes (DEGs), similar time-point-related differential expression profile of genes, and similar NtCBF gene co-expression modules, suggesting conservation of adaptation strategies for cold responses. Importantly, we found that YT experienced DEGs even under normal growth condition and had less DEGs in early stage of cold stress (0.5-2 h) when compared to TT, reflecting occurrence of genotype-dependent gene transcription. Moreover, a gene co-expression module (brown) with stress-related genes up-regulated in YT instead of TT at late stage (4-8 h), which might contribute to contrasting phenotypic changes during cold stress between TT and YT. Conclusions: our study provides valuable resources for transcriptomic studies of cold responses in plants. It also helps to identify key cold responsive genes for genetic manipulation for breeding of tobacco cultivars in the future.
2022-08-03 | GSE173352 | GEO
Project description:Cigarette smoke (CS) is affecting considerably the oral mucosa. Heating, instead of burning, tobacco reduces consistently the amount of toxic compounds and may exert a lower impact on oral health than combusted cigarettes. The carbon-heated tobacco product 1.2 (CHTP1.2) is a potential modified risk tobacco product (MRTP) based on heat-not-burn technology. Using a systems toxicology assessment framework, we compared the effects of exposure to CHTP1.2 aerosol with those of CS from a reference cigarette (3R4F). Human organotypic cultures derived from buccal and gingival epithelia were exposed acutely (28-min) or repeatedly (28 min/day for 3 days), respectively, to two matching concentrations of CHTP1.2 aerosol or 3R4F CS, and a non-diluted (100%) CHTP1.2 aerosol. The results showed an absence of cytotoxicity, reduction in pathophysiological alterations, toxicological marker proteins, and inflammatory mediators following exposure to CHTP1.2 aerosol compared with 3R4F CS. Changes in mRNA and miRNA expression were linked by an integrative analysis approach, suggesting a regulatory role of miRNAs in several smoke/disease-relevant biological processes induced by 3R4F CS. The identification of mechanisms by which potential MRTPs can reduce the impact of tobacco use on biological systems is of great importance in understanding the molecular basis of the smoking harm reduction paradigm.
2018-03-07 | E-MTAB-6542 | biostudies-arrayexpress
Project description:Cigarette smoke (CS) is affecting considerably the oral mucosa. Heating, instead of burning, tobacco reduces consistently the amount of toxic compounds and may exert a lower impact on oral health than combusted cigarettes. The carbon-heated tobacco product 1.2 (CHTP1.2) is a potential modified risk tobacco product (MRTP) based on heat-not-burn technology. Using a systems toxicology assessment framework, we compared the effects of exposure to CHTP1.2 aerosol with those of CS from a reference cigarette (3R4F). Human organotypic cultures derived from buccal and gingival epithelia were exposed acutely (28-min) or repeatedly (28 min/day for 3 days), respectively, to two matching concentrations of CHTP1.2 aerosol or 3R4F CS, and a non-diluted (100%) CHTP1.2 aerosol. The results showed an absence of cytotoxicity, reduction in pathophysiological alterations, toxicological marker proteins, and inflammatory mediators following exposure to CHTP1.2 aerosol compared with 3R4F CS. Changes in mRNA and miRNA expression were linked by an integrative analysis approach, suggesting a regulatory role of miRNAs in several smoke/disease-relevant biological processes induced by 3R4F CS. The identification of mechanisms by which potential MRTPs can reduce the impact of tobacco use on biological systems is of great importance in understanding the molecular basis of the smoking harm reduction paradigm.
2018-03-07 | E-MTAB-6537 | biostudies-arrayexpress