Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma
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PROVIDER: EGAS00001004430 | EGA |
REPOSITORIES: EGA
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Project description:Oropharyngeal squamous cell carcinoma (OPSCC) is diagnosed in 93,000 patients worldwide per year and 51,000 annual deaths can be attributed to this disease. OPSCCs are either human papillomavirus associated (HPV-positive) cancers or non-virally induced, primarily tobacco and alcohol associated (HPV-negative) cancers. MS analysis enabled the identification of naturally HLA-presented peptides in OPSCC tumor tissue. By comparative profiling against benign HLA ligandomic datasets, we demonstrated that tumor-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi-) personalized strategies.
2023-02-27 | PXD033383 | Pride
Project description:Background: Human papillomavirus-16 (HPV) causes the majority of oropharyngeal squamous cell carcinomas (OPSCC), especially tonsillar and base of tongue cancer. HPV-positive cancer patients have better clinical outcomes than HPV-negative patients and several groups have suggested de-intensification of treatment schedules in order to avoid unnecessary side effects in the former group. Current TNM classification falls short in predicting OPSCC patients’ prognosis highlighting the unmet need for novel biomarkers. Here we tested the expression and the prognostic role of microRNAs (miRs) in relation to HPV status and clinical outcome in 220 patients with OPSCC distributed in three independent cohorts. Methods: MiR expression was assessed in three cohorts of OPSCC patients by NanoString nCounter Technology (training; n=78), Real-Time PCR (validation; n=93) and miR-Sequencing (TCGA; n=51). In-Situ Hybridization was used to define miR localization. Differences in progression free (PFS) and overall survival (OS) according to miR expression were assessed using the Kaplan-Meier method and compared using the log rank test. Univariate and multivariate analyses using Cox proportional hazards method established the relationship between miR expression, HPV-status, clinical-pathological variables and survival. Results: miR-155 and miR-193b-3p were dysregulated in HPV-negative compared to HPV-positive OPSCC. MiR-193b-3p up-regulation was associated with worse PFS and OS in the training and validation cohorts and the TCGA cohort respectively. MiR-193b-3p prognostic effect was independent of HPV-status. Among HPV-positive patients, over-expression of miR-301b and down-modulation of miR-185b correlated with improved survival. Conclusion: Expression analysis for specific miRs in combination with tumor HPV-status and clinical-pathological variables may be useful in the prediction of clinical outcome for OPSCC patients.
2017-01-01 | GSE82064 | GEO
Project description:Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increases the risk of breast cancer. Little is known, however, about the molecular mechanisms by which tobacco smoke contributes to breast carcinogenesis. To investigate these mechanisms we have analyzed gene expression and methylation in MCF 10A mammary epithelial cells chronically exposed to aqueous cigarette smoke extract (CSE).
2013-08-12 | GSE42667 | GEO
Project description:Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increases the risk of breast cancer. Little is known, however, about the molecular mechanisms by which tobacco smoke contributes to breast carcinogenesis. To investigate these mechanisms we have analyzed gene expression and methylation in MCF 10A mammary epithelial cells chronically exposed to aqueous cigarette smoke extract (CSE).
2013-08-12 | GSE42623 | GEO
Project description:Cigarette smoking exerts diverse physiological effects including immune suppression. Existing US epidemiological data show that consumption of smokeless tobacco products, such as moist snuff, is less harmful relative to cigarette smoking. In efforts to understand the molecular changes due to consumption of different tobacco product classes, we have shown recently that smokers exhibit distinct peripheral blood mononuclear cells (PBMCs) gene expression patterns relative to moist snuff users and non-tobacco consumers (NTCs). To better characterize the biological effects exerted from the use of different tobacco products, a genome-wide gene expression study, using a cultured PBMC model, was performed. Global gene expression profiling results showed that 5,421 genes (2,809 upregulated and 2,612 downregulated) were dose-dependently changed by WSCM (pFDR < 0.01). Some gene expression changes detected in the cultured system were also observed in clinical studies. For example, FEZ1 and SLAMF7 were suppressed by WSCM while CCR2 and HHEX genes were upregulated by WSCM commonly in the cultured experiment and clinical studies. WSCM exposures, but not STE, uniquely affected genes involved in immune cell development and inflammatory response. Ingenuity Pathway Analysis identified upstream regulators, such as TNF, IL1β, and NFκB to be likely responsible for the observed gene expression changes and that these cascading signals were generally suppressed by WSCM, but not STE. Collectively, these findings sµggested that combustible and non-combustible tobacco products produce distinct biological effects which could explain the observed chronic immune suppression in smokers.
2019-02-25 | GSE110027 | GEO
Project description:Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and despite therapeutic advances, late-stage diagnoses continue to negatively affect survival, presenting a continuing challenge for clinicians. Detailed molecular characterization by recent bulk and single-cell RNA-sequencing datasets from OSCC suggest that identification of prognostic biomarkers may lead to more targeted therapies, improving patient outcomes. Development of OSCC is associated with exposure to tobacco, alcohol consumption, and infection with human papillomavirus. The mouse model of 4-Nitroquinoline 1-oxide (4NQO) carcinogenesis produces a spectrum of neoplastic lesions that are a robust model of tobacco-induced OSCC. Specifically, studies have shown that similar to human OSCC, mouse OSCC shows upregulation of the oncogenic master transcription factor p63. We performed complementary loss- and gain-of-function experiments of p63 in mouse 4NQO-transformed OSCC cell lines and utilized RNA-sequencing and ChIP-sequencing to uncover the p63 oncogenic network. By combining our signature with publicly available bulk and scRNA-seq data, we generated a murine p63 signature that we have utilized to better understand the role of p63 in mOSCC. Our analyses have identified several potential biomarkers and conserved pathways that are relevant to hOSCC, as well as highlighted the dynamic role of p63 in migration and invasion.
2023-01-10 | GSE217669 | GEO
Project description:Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and despite therapeutic advances, late-stage diagnoses continue to negatively affect survival, presenting a continuing challenge for clinicians. Detailed molecular characterization by recent bulk and single-cell RNA-sequencing datasets from OSCC suggest that identification of prognostic biomarkers may lead to more targeted therapies, improving patient outcomes. Development of OSCC is associated with exposure to tobacco, alcohol consumption, and infection with human papillomavirus. The mouse model of 4-Nitroquinoline 1-oxide (4NQO) carcinogenesis produces a spectrum of neoplastic lesions that are a robust model of tobacco-induced OSCC. Specifically, studies have shown that similar to human OSCC, mouse OSCC shows upregulation of the oncogenic master transcription factor p63. We performed complementary loss- and gain-of-function experiments of p63 in mouse 4NQO-transformed OSCC cell lines and utilized RNA-sequencing and ChIP-sequencing to uncover the p63 oncogenic network. By combining our signature with publicly available bulk and scRNA-seq data, we generated a murine p63 signature that we have utilized to better understand the role of p63 in mOSCC. Our analyses have identified several potential biomarkers and conserved pathways that are relevant to hOSCC, as well as highlighted the dynamic role of p63 in migration and invasion.
2023-01-10 | GSE217668 | GEO
Project description:Head and neck cancer (HNC) is the fifth most common malignancy worldwide with an annual mortality rate of 200,000. About 90% of HNC can be classified as head and neck squamous cell carcinomas (HNSCC), of which approximately 75% are attributed to alcohol and tobacco consumption and 25% are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct. African American (AA) males have a higher incidence of HNC than any other racial/gender group, and a mortality rate almost three-fold that observed in European American (EA) males. Overall, AA patients tend to present with more HPV-negative OPC and have worse prognosis as compared to both HPV-positive and HPV-negative HNSCC in EA patients. Despite the unveiling of differential gene expression patterns, genetic and epigenetic profiles and the compilation of a mutational landscape along with preliminary TCGA data of HPV-related and unrelated HNC, the molecular determinants of the racial disparity in HNC are yet to be identified. This study aimed to compare the gene expression profiles of HPV-negative HNSCC from AA and EA patients, and determine their biological differences. ANALYSIS 2: Two-condition, on-color experiment: African American (AA) vs European American (EA) HPV-negative oropharyngeal squamous cell carcinomas. Biological replicates: 8 African American and 8 European American.
2014-03-05 | E-GEOD-55543 | biostudies-arrayexpress
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:HPV-positive oral squamous cell carcinomas (OSCCs) are specific biological and clinical entities, characterized by a more favorable prognosis compared to HPV-negative OSCCs and occurring generally in non-smoking and non-drinking younger individuals. However, poor information is available on the molecular and the clinical behavior of HPV-positive oral cancers occurring in smoking/drinking subjects. Thus, this study was designed to compare, at molecular level, two OSCC cell lines, both derived from drinking and smoking individuals and differing for presence/absence of HPV infection.
2019-12-01 | E-MTAB-6152 | biostudies-arrayexpress