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
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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 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: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:Protease activity has been associated with pathological processes that can lead to cancer development and progression. However, understanding the pathological unbalance in proteolysis is challenging since changes can occur simultaneously at protease, their inhibitor and substrate levels. In this work we combined peptidomics, proteomics and peptidase predictions for studying proteolytic events in saliva associated with oral squamous cell carcinoma (OSCC) prognosis. Our results suggest that cleavage products differentially abundant in the saliva of patients with (N+) or without (N0) nodal metastasis exhibit potential of prognostic value in oral cancer and were are able to discriminate N+ and N0 patients whereas reduced protein levels of peptidase inhibitors might disturb the proteolytic balance in saliva of OSCC patients with poor prognosis
2020-11-13 | PXD020211 | Pride
Project description:Protease activity has been associated with pathological processes that can lead to cancer development and progression. However, understanding the pathological unbalance in proteolysis is challenging since changes can occur simultaneously at protease, their inhibitor and substrate levels. Here, we present a pipeline that combines peptidomics, proteomics and peptidase predictions for studying proteolytic events in saliva associated with oral squamous cell carcinoma (OSCC) prognosis and lymph node metastasis. Our results suggest that cleavage products differentially abundant in the saliva of patients with (N+) or without (N0) nodal metastasis exhibit potential of prognostic value in oral cancer whereas reduced levels of peptidase inhibitors disturb the proteolytic balance in saliva of OSCC patients with worse prognosis.
2020-11-13 | PXD020111 | Pride
Project description:Background: The differential abundance of cell-free RNAs in bodily fluids is emerging as a promising tool for the non-invasive molecular diagnosis of cancer. Human saliva is considered a promising source of non-invasive biomarkers of diagnostic value for oral cancer detection. This study aims to identify diagnostic potent salivary RNAs in oral squamous cell carcinoma (OSCC)-patients by RNA-Sequencing. Method: Unstimulated saliva was collected from 5 normal control (NC) individuals and 9 OSCC patients (PS) with prior consent and ethical committee approvals. Total RNA isolated from cell-free saliva (CFS) supernatant was used to prepare small RNA libraries and sequenced on the Ion Torrent S5 platform. The sequencing reads were aligned to the human genome (hg19) using Bowtie 2, and the differential expression analysis was performed using RUVSeq and DESeq2. Mapped reads were screened across miRBase (v22) annotations for miRNAs and Gencode (v19) annotation for other RNAs. Reads were quantified by the Featurecount (v1.4.6) module of the R-package. The microbial-RNA enrichment analysis was determined using the One Codex platform. Result: RNA-sequencing detected protein-coding transcripts (PCTs), long-intergenic RNAs (lincRNAs), microRNAs (miRNAs), small nuclear RNAs (snRNAs), transfer RNAs (tRNAs) and pseudogenes from the saliva of PS and HC samples. Transcriptome analyses revealed 89 PCTs, 18 lincRNAs and 6 miRNAs differentially expressed between PS and HC with a log2fold change ≥ 1 or ≤ -1 and p-value < 0.05. Gene ontology and pathway enrichment analyses indicated a significant correlation of the identified PCTs and miRNAs to various cancer-related pathways that may have implications in the pathogenesis of OSCC. Interestingly, unmapped non-human reads aligned to the microbial reference genomes. Further analyses of these microbial sequence reads revealed a significant microbial dysbiosis differentiating PS from HC. Metabolic pathways and functional analysis of the identified microbial phylotypes showed gene ontologies associated with inflammation, cell proliferation, ROS generation, and a range of metabolic processes. Conclusion: We report novel panels of differentially expressed PCTs, miRNAs and lincRNAs distinguishing PS from HC. Importantly, our results also provide evidence for oral microbial dysbiosis that appears to have pathological implications in OSCC. Summarily, this study provides a comprehensive landscape of salivary RNAs that can be exploited as non-invasive biomarkers for OSCC detection.
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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 cavity cancer is one of the most common cancer worldwide and oral cavity squamous cell carcinoma (OSCC) accounts for up to 90 percent of oral cancers. In Taiwan, OSCC is the fifth most common malignancy of male and causes more than 250 deaths per year. The poor outcome of OSCC patients is principally ascribed to the fact that this disease is often advanced at the time of diagnosis, suggesting that early detection and prevention of OSCC are urgently needed to reduce the cancer burden. Analysis of cancer-related body fluids is one of promising approaches to identify cancer-related molecules and biomarker candidates. To identify salivary biomarkers of OSCC, salivary samples of OSCC patients, individuals with oral potentially malignant disorders (OPMD), and healthy volunteers were collected. With isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry (MS) analysis, 1838 proteins were identified. The levels of 102 proteins are found to be elevated in the saliva samples of OSCC patients compared to that of OPMD and healthy groups. To improve the feasibility of biomarkers, we used a two-phase verification to measure these candidates. Among them, salivary levels of AHSG, CFH, FGA, and SERPINA1 were determined to be significantly higher in the OSCC patients than in the healthy or in the OPMD group with both of MRM-MS and ELISA. Furthermore, the levels of these proteins were highly related to tumor size, lymph-node metastasis, and cancer stages. The results of this study not only provides a powerful strategy for verification of biomarker candidates, but also suggested that AHSG, CFH, FGA, and SERPINA1 could act as salivary biomarkers for OSCC detection.
2019-08-15 | PXD008655 | Pride
Project description:Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco- and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ~65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome towards PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage.
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