Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Differences in Extracellular Vesicle Protein Cargo Are Dependent on Head and Neck Squamous Cell Carcinoma Cell of Origin and Human Papillomavirus Status.

ABSTRACT: To identify potential extracellular vesicle (EV) biomarkers in head and neck squamous cell carcinoma (HNSCC), we evaluated EV protein cargo and whole cell lysates (WCL) from HPV-positive and -negative HNSCC cell lines, as well as normal oral keratinocytes and HPV16-transformed cells. EVs were isolated from serum-depleted, conditioned cell culture media by polyethylene glycol (PEG) precipitation/ultracentrifugation. EV and WCL preparations were analyzed by LC-MS/MS. Candidate proteins detected at significantly higher levels in EV compared with WCL, or compared with EV from normal oral keratinocytes, were identified and confirmed by Wes Simple Western protein analysis. Our findings suggest that these proteins may be potential HNSCC EV markers as proteins that may be (1) selectively included in EV cargo for export from the cell as a strategy for metastasis, tumor cell survival, or modification of tumor microenvironment, or (2) representative of originating cell composition, which may be developed for diagnostic or prognostic use in clinical liquid biopsy applications. This work demonstrates that our method can be used to reliably detect EV proteins from HNSCC, normal keratinocyte, and transformed cell lines. Furthermore, this work has identified HNSCC EV protein candidates for continued evaluation, specifically tenascin-C, HLA-A, E-cadherin, EGFR, EPHA2, and cytokeratin 19.

SUBMITTER: Goudsmit C

PROVIDER: S-EPMC8345072 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

More than a Bubble: Extracellular Vesicle microRNAs in Head and Neck Squamous Cell Carcinoma.

Project description:MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play a pivotal regulatory role in a broad variety of biological processes. Dysregulation of miRNAs is associated with several human diseases, particularly cancer. Extracellular vesicles (EVs) are crucial components in intercellular communication. As part of the cargo of EVs, miRNAs are involved in EV-mediated cell-to-cell interactions, including promotion or suppression of tumor development. The knowledge on the molecular mechanisms and clinical importance of EV-miRNAs in head and neck squamous cell carcinoma (HNSCC) has rapidly grown over the past years. In the present review, the current understanding regarding the effect of EV-miRNAs on HNSCC tumorigenesis is summarized, which includes effects on tumor proliferation, angiogenesis, invasion and metastasis, the tumor microenvironment, immune modulation, and treatment resistance. EV-miRNA-based biomarkers in liquid biopsies such as blood and saliva may open up new possibilities for employing EV-miRNAs for screening and early diagnostics as well as disease monitoring. Future perspectives include the promise of EV-miRNAs as a novel therapeutic target.

| S-EPMC8909139 | biostudies-literature

Extracellular Vesicle-Based Drug Delivery Systems for Head and Neck Squamous Cell Carcinoma: A Systematic Review.

Project description:It is estimated that there are over 890,000 new cases of head and neck squamous cell carcinoma (HNSCC) worldwide each year, accounting for approximately 5% of all cancer cases. Current treatment options for HNSCC often cause significant side effects and functional impairments, thus there is a challenge to discover more acceptable treatment technologies. Extracellular vesicles (EVs) can be utilized for HNSCC treatment in several ways, for example, for drug delivery, immune modulation, as biomarkers for diagnostics, gene therapy, or tumor microenvironment modulation. This systematic review summarizes new knowledge regarding these options. Articles published up to 11 December 2022, were identified by searching the electronic databases PubMed/MEDLINE, Scopus, Web of Science, and Cochrane. Only full-text original research papers written in English were considered eligible for analysis. The quality of studies was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies, modified for the needs of this review. Of 436 identified records, 18 were eligible and included. It is important to note that the use of EVs as a treatment for HNSCC is still in the early stages of research, so we summarized information on challenges such as EV isolation, purification, and standardization of EV-based therapies in HNSCC.

| S-EPMC10223025 | biostudies-literature

Prognostic implications of human papillomavirus status for patients with non-oropharyngeal head and neck squamous cell carcinomas.

Project description:PurposeWe examined overall survival in a large cohort of patients with human papillomavirus (HPV)-positive and HPV-negative non-oropharyngeal squamous cell carcinoma of the head and neck (non-OPSCC).MethodsPatients diagnosed with non-OPSCC and known HPV status were identified in the National Cancer Database (NCDB). Multivariate logistic regression was applied to examine factors associated with HPV status. Multivariate analysis was utilized to determine factors correlated with overall survival. Propensity score-weighted Kaplan-Meier estimation was used to adjust for confounders in survival analyses. Multiple imputation method was used for sensitivity analysis.ResultsWe identified 19,993 non-OPSCC patients with 5070 being positive for HPV in the NCDB. Median follow-up was 23.5 months. HPV-positive patients were more commonly male, white, with a lower comorbidity index score, presenting with T-stage <2, and N-stage ≥1. Unadjusted 3-year overall survival was 62% and 80% for HPV-negative and HPV-positive patients, respectively (p < 0.0001). On multivariate analysis, mortality was reduced for HPV-positive patients with early stage (HR = 0.68) and locally advanced disease (HR = 0.46). Adjusted 3-year overall survival was 65% for HPV-negative and 76% for HPV-positive patients (p < 0.0001). The survival advantage of HPV was maintained in all subsites and robust on sensitivity analysis.ConclusionsPatients with HPV-positive non-OPSCC exhibit similar characteristics as HPV-positive OPSCC. Overall survival was significantly higher for patients with HPV-positive versus HPV-negative non-OPSCC. These data reveal that HPV-positive non-OPSCC represent a favorable cohort that warrants recognition in the design of future clinical trial investigation.

| S-EPMC7069668 | biostudies-literature

Plasma extracellular vesicle microRNA-491-5p as diagnostic and prognostic marker for head and neck squamous cell carcinoma.

Project description:Poor survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is partly due to early diagnosis difficulties and the lack of reliable biomarkers for predicting treatment outcomes. In the discovery cohort, plasma-derived extracellular vesicles (EVs) from LA-HNSCC patients (n = 48) and healthy volunteers (n = 12) were used for profiling for microRNA (miRNA) expression by NanoString analysis. Ten EV-associated miRNAs were differentially expressed between LA-HNSCC patients and healthy volunteers. Subsequently, the results were validated in the individual discovery and additional cases (HNSCC, n = 73; control, n = 20) by quantitative RT-PCR. Among 10 EV-miRNAs, four (miR-27b-3p, miR-491-5p, miR-1910-5p, and miR-630) were significantly dysregulated in LA-HNSCC patients (n = 73) compared with healthy volunteers (n = 20). The miRNA prediction models were developed to discriminate HNSCC patients from healthy volunteers. The model using miR-491-5p was selected as a diagnostic biomarker for LA-HNSCC with a sensitivity and specificity of 46.6% and 100%, respectively (P < .001). The dynamic changes of miRNA model score (ΔmiRNAs) were determined using scores pre- and postdefinitive treatment to further investigate the prognostic value of miRNA prediction models. The univariate and multivariate analyses indicated that ΔmiR-491-5p was the most powerful and independent prognostic indicator for overall survival (hazard ratio [HR] 5.66, 95% confidence interval, 1.77-18.01; P = .003) and disease-free survival (HR 2.82, 95% CI, 1.13-7.05; P = .027) of HNSCC patients. In summary, the miR-491-5p prediction model could serve as a blood-based diagnostic marker for LA-HNSCC. Moreover, ΔmiR-491-5p could be a potential monitoring prognostic marker to reflect the survival of HNSCC patients.

| S-EPMC8486186 | biostudies-literature

Relative Biological Effectiveness of Carbon Ions for Head-and-Neck Squamous Cell Carcinomas According to Human Papillomavirus Status.

Project description:Carbon-ion radiotherapy (CIRT) has strong antitumor effects and excellent dose conformity. In head-and-neck squamous cell carcinoma (HNSCC), human papillomavirus (HPV) status is a prognostic factor for photon radiotherapy outcomes. However, the effect of HPV status on the sensitivity of HNSCCs to carbon ions remains unclear. Here, we showed that the relative biological effectiveness (RBE) of carbon ions over X-rays was higher in HPV-negative cells than in HSGc-C5 cells, which are used for CIRT dose establishment, whereas the RBE in HPV-positive cells was modest. These data indicate that CIRT is more advantageous in HPV-negative than in HPV-positive HNSCCs.

| S-EPMC7565683 | biostudies-literature

p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma.

Project description:PurposeAlthough p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx.Patients and methodsp16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics.Resultsp16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes.ConclusionSimilar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.

| S-EPMC4251957 | biostudies-literature

Molecular Diagnostics in Human Papillomavirus-Related Head and Neck Squamous Cell Carcinoma.

Project description:The incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinoma continues to increase. Accurate diagnosis of the HPV status of a tumor is vital, as HPV+ versus HPV- tumors represent two unique biological and clinical entities with different treatment strategies. High-risk HPV subtypes encode oncoproteins E6 and E7 that disrupt cellular senescence and ultimately drive tumorigenesis. Current methods for detection of HPV take advantage of this established oncogenic pathway and detect HPV at various biological stages. This review article provides an overview of the existing technologies employed for the detection of HPV and their current or potential future role in management and prognostication.

| S-EPMC7072739 | biostudies-literature

New insights into human papillomavirus-associated head and neck squamous cell carcinoma.

Project description:Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an entity with peculiar clinical and molecular characteristics, which mainly arises from the reticulated epithelium lining the crypts of the palatine tonsils and the base of the tongue. The only head and neck site with a definite etiological association between persistent high-risk (HR) HPV infection and development of SCC is the oropharynx. HPV-positive malignancies represent 5-20% of all HNSCCs and 40-90% of those arising from the oropharynx, with widely variable rates depending on the geographic area, population, relative prevalence of environment-related SCC and detection assay. HPV-16 is by far the most common HR HPV genotype detected in oropharyngeal SCC (OPSCC), and the only definitely carcinogenic genotype for the head and neck region. Patients with HPV-induced OPSCC are more likely to be middle-aged white men, non-smokers, non-drinkers or mild to moderate drinkers, with higher socioeconomic status and better performance status than subjects with HPV-unrelated SCC. HPV-induced HNSCCs are often described as non-keratinizing, poorly differentiated or basaloid carcinomas, and are diagnosed in earlier T-category with a trend for a more advanced N-category, with cystic degeneration, than the HPV-unrelated carcinomas. HPV positivity is associated with better response to treatment and modality-independent survival benefit. Treatment selection in HPV-related oropharyngeal carcinoma is becoming a critical issue, and although there is no evidence from randomized, controlled trials to support a treatment de-escalation in HPV-positive SCC, some investigators argue that intensive combined modality strategies may represent an overtreatment.

| S-EPMC3665382 | biostudies-literature

Oral health and human papillomavirus-associated head and neck squamous cell carcinoma.

Project description:BackgroundIndicators of poor oral health, including smoking, have been associated with increased risk of head and neck squamous cell carcinoma, especially oropharyngeal squamous cell carcinoma (OPSCC), yet few studies have examined whether this association is modified by human papillomavirus (HPV) status.MethodsData from interviews and tumor HPV status from a large population-based case-control study, the Carolina Head and Neck Cancer Study (CHANCE), were used to estimate the association between oral health indicators and smoking among 102 HPV-positive patients and 145 HPV-negative patients with OPSCC and 1396 controls. HPV status was determined by p16INK4a (p16) immunohistochemistry. Unconditional, multinomial logistic regression was used to estimate odds ratios (ORs) for all oral health indictors adjusting for important covariates.ResultsRoutine dental examinations were associated with a decreased risk of both HPV-negative OPSCC (OR, 0.52; 95% confidence interval [CI], 0.35-0.76) and HPV-positive OPSCC (OR, 0.55; 95% CI, 0.36-.86). Tooth mobility (a proxy for periodontal disease) increased the risk of HPV-negative disease (OR, 1.70; 95% CI, 1.18-2.43) slightly more than the risk for HPV-positive disease (OR, 1.45; 95% CI, 0.95-2.20). Ten or more pack-years of cigarette smoking were strongly associated with an increased risk of HPV-negative OPSCC (OR, 4.26; 95% CI, 2.85-6.37) and were associated less with an increased risk of HPV-positive OPSCC (OR, 1.62; 95% CI, 1.10-2.38).ConclusionsAlthough HPV-positive and HPV-negative HNSCC differ significantly with respect to etiology and tumorigenesis, the current findings suggest a similar pattern of association between poor oral health, frequency of dental examinations, and both HPV-positive and HPV-negative OPSCC. Future research is required to elucidate interactions between poor oral health, tobacco use, and HPV in the development of OPSCC. Cancer 2017;71-80. © 2016 American Cancer Society.

| S-EPMC5161679 | biostudies-literature