Expression profiling of HPV+ Patient Derived Xenografts (PDXs) by high throughput sequencing
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE193388 | GEO | 2025/01/10
REPOSITORIES: GEO
Similar Datasets
Project description:The incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has increased more than 200% in the past 20 years. Recent genetic sequencing efforts have elucidated relevant genes in head and neck cancer, but HPV-related tumors have consistently shown few DNA mutations. In this study, we sought to analyze alternative splicing events (ASE) that could alter gene function independent of mutations. To identify ASE unique to HPV-related tumors, RNA sequencing was performed on 46 HPV-positive OPSCC and 25 normal tissue samples. A novel algorithm using outlier statistics on RNA-sequencing junction expression identified 109 splicing events, which were confirmed in a validation set from The Cancer Genome Atlas.
2018-03-20 | GSE112026 | GEO
Project description:The incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has increased more than 200% in the past 20 years. Recent genetic sequencing efforts have elucidated relevant genes in head and neck cancer, but HPV-related tumors have consistently shown few DNA mutations. In this study, we sought to analyze alternative splicing events (ASE) that could alter gene function independent of mutations. To identify ASE unique to HPV-related tumors, RNA sequencing was performed on 46 HPV-positive OPSCC and 25 normal tissue samples. A novel algorithm using outlier statistics on RNA-sequencing junction expression identified 109 splicing events, which were confirmed in a validation set from The Cancer Genome Atlas.
2018-03-20 | GSE112023 | GEO
Project description:The global rise of HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) has generated considerable interest underlying its etiology and management. Despite an overall decline in head and neck malignancies, the incidence in OPSCC has by contrast sharply risen, with HPV(+) subtypes now comprising 80% of all OPSCC.1,2 Relative to HPV(-) OPSCC, HPV(+) patients are more responsive to chemoradiation and harbor a 52% risk-of-death reduction.3 Despite this distinct outcome, treatment regimens remain the same for all OPSCC subtypes (smoking-driven and virus-driven), rather than an adaptive approach to what most consider distinct diseases. The short-term effects (e.g., mucositis, odynophagia) and long-term toxicities (e.g., xerostomia, dysphagia, ototoxicity) from treatment substantially affect quality of life, and rival the impact of the cancer itself. Recently published as well as ongoing trials are actively examining deintensification approaches2,4-9, with the goal of diminishing treatment sequelae for HPV(+) subtypes. While deintensification may decrease chemoradiation-related toxicities, it nonetheless may also undertreat a meaningful percentage of HPV(+) patients who may then recur. In examining national trials, 19% of HPV(+) patients had disease progression after therapy, with a two-year survival rate of 60%.10 Current methods to ascertain HPV status involve p16 staining. However, on comparison with gold standard E6/E7 expression by qPCR, p16 harbored a 15% false positivity rate11, suggesting limited utility as a sole biomarker for deintensification. Improved molecular stratification would greatly enhance the clinician’s ability to precisely tailor treatment while minimizing the risk of jeopardizing outcomes. One approach encompasses in-depth proteomic profiling of HPV(+) OPSCC to reveal distinct protein expression profiles and delineate clinically relevant upstream pathways. In turn, these proteomic differences may distinguish higher-risk disease (cases predisposed to recurrence that may benefit from treatment intensification) from lower-risk phenotypes (cases whose treatment response is sufficiently robust to warrant deintensification). Here, two HPV(+) OPSCC cohorts stratified by treatment response are compared via a hybrid data dependent acquisition/data independent acquisition (DDA/DIA) approach via mass spectrometry. We focused on detection of low-abundance proteins to highlight proteomic signatures that can be potentially exploited for treatment stratification.
2022-05-05 | PXD028618 | Pride
Project description:Oropharyngeal squamous cell carcinoma (OPSCC), a distinct head and neck cancer subtype that develops in the oropharynx, is well known to be categorized into human papillomavirus induced (HPV+) and non-HPV induced (HPV-). While HPV+ OPSCC is reported to be clinically advantageous compared to HPV- OPSCC, the heterogeneous responses in HPV+ OPSCC during immunotherapy treatment have not been well characterized at the molecular level. In this study, we assess both tumor and immune cells of the OPSCC tumor microenvironment (TME) via single-cell RNA sequencing (scRNA-seq) and single-cell TCR sequencing (scTCR-seq). By dissecting the transcriptome of OPSCC tumor cells, we find that cancer cell transcriptional diversity may be a strong factor in negating HPV associated clinical benefits. By assessing immune cells, we observed molecular antiviral and anti-tumor characteristics of T cells that is associated with HPV infection, and key cell-cell interaction differences among resident memory T cells (Trm), follicular helper T cells, and B cells. Importantly, we identify a novel molecular state within the HPV+ OPSCC that is distinguished by the expression KLRB1 (CD161) in the Trm that inhibits anti-tumor activity, which may further explain the heterogeneous clinical benefits of HPV+OPSCC. Association of KLRB1 expression of Trm and immunotherapy outcome was confirmed via immunofluorescence analysis, suggesting CD161 as a novel therapeutic target to improve cancer treatment of HPV+ OPSCC.
2024-06-01 | GSE226620 | 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: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:Expression profiling of HPV+ Patient Derived Xenografts (PDXs) by high throughput sequencing
| PRJNA796005 | ENA
Project description:Oropharyngeal cancers have 2 main etiologies : High risk HPV (human papilloma virus) and tobacco/alcohol. The aim of this work is to find a miRNA signature specific to HPV induced oropharyngeal cancers
2015-05-12 | E-MTAB-3410 | 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: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