DNA methylation analysis in oropharyngeal cancer [EPIC array]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE124632 | GEO | 2020/01/20
REPOSITORIES: GEO
Similar Datasets
Project description:DNA methylation analysis in oropharyngeal squamous carcinoma (OPSCC) samples and oropharyngeal non-cancerous mucosa samples. Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across 485,577 CpG sites. Total samples included 89 OPSCC samples and 5 non-cancerous mucosa samples.
2020-01-20 | GSE124464 | GEO
Project description:DNA methylation analysis in oropharyngeal squamous carcinoma(OPSCC) samples, oropharyngeal non-cancerous mucosa samples and head and neck cancer cell lines, FaDu and UMSCC47 before and after 5-aza'2-deoxycytidine(Aza)/trichostatin A(TSA) treatment. Infinium HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across 485,577 CpG sites. Samples included 13 OPSCC samples, 4 non-cancerous mucosa samples and 2 FaDu with and without Aza/TSA treatment and 2 UMSCC47 with and without Aza/TSA treatment.
2018-05-10 | GSE98807 | GEO
Project description:Upper aerodigestive tract (UADT) tumors present different biological behavior and prognosis, suggesting specific molecular mechanisms underlying their development. However, they are rarely considered as single entities (particularly head and neck subsites) and share the most common genetic alterations. Therefore, there is a need for a better understanding of the global DNA methylation differences among UADT tumors. We performed a genome-wide DNA methylation analysis of esophageal (ESCC), laryngeal (LSCC), oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas, and their non-tumor counterparts. The unsupervised analysis showed that non-tumor tissues present markedly distinct DNA methylation profiles, while tumors are highly heterogeneous. Hypomethylation was more frequent in LSCC and OPSCC, while ESCC and OSCC presented mostly hypermethylation, with the latter showing a CpG island overrepresentation. Differentially methylated regions affected genes in 127 signaling pathways, with only 3.1% of these being common among different tumor subsites, but with different genes affected. The WNT signaling pathway, known to be dysregulated in different epithelial tumors, is a frequent hit for DNA methylation and gene expression alterations in ESCC and OPSCC, but mostly for genetic alterations in LSCC and OSCC. UADT tumor subsites present differences in genome-wide methylation regarding their profile, intensity, genomic regions and signaling pathways affected.
2021-07-08 | GSE178219 | GEO
Project description:Genome-wide DNA methylation profiling of over 850,000 methylation sites carried out using the Illumina MethylationEPIC BeadChip was used to compare 18 babies born with congenital Zika virus microcephaly, 7 babies exposed to Zika virus in utero but born without clinical signs, and 20 control unexposed unaffected babies
2020-07-20 | GSE145233 | GEO
Project description:Using MCIp, we enriched highly methylated DNA from a normal mucosa control and from three OPSCC patient subgroups regarding the HPV status: group A, DNA-RNA- (Tu1-Tu5); group B, DNA+RNA- (Tu6-Tu10); group C, DNA+RNA+ (Tu11-Tu15). 3 groups of tumor biopsies, 5 samples each regarding HPV status: DNA-RNA-, DNA+RNA-, DNA+RNA+ and a control sample (normal mucosa from healthy individual): 15 tumor samples/ 1 control sample
2013-09-16 | E-GEOD-41152 | biostudies-arrayexpress
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:Nowadays, risk stratification for oropharyngeal squamous cell carcinoma (OPSCC) is based on HPV status, tobacco smoking, and tumor stage. Although HPV positivity represents a strong prognostic factor for both reduced risk of relapse, and improved survival, there is a subset of HPV-positive OPSCC patients who still experience poor outcomes. Furthermore, HPV-negative OPSCC patients, who have an even higher risk of relapse within two years from the end of the treatment, are still lacking suitable prognostic biomarkers for clinical outcome. In this scenario, inclusion of new biomarkers that differentiate OPSCC patients with a diverse prognosis is urgently needed. Since genes encoding for epigenetic regulators have been frequently found mutated in several tumors, including OPSCC, it is expected that epigenetic changes may play a major role in OPSCC pathogenesis and response to therapy. Consistently, HPV oncoproteins have been also demonstrated to impact on epigenetic pattern by interacting with different epigenetic regulators, thus affecting the chromatin landscape of OPSCC HPV-positive cells. Along this line, we have recently demonstrated the methylation levels of the “Long interspersed nucleotide element-1” (LINE-1) repetitive elements, a widely accepted surrogate of overall genomic DNA methylation content, was different between HPV16-positive and -negative OPSCC patients. In particular, the lowest level of LINE-1 element methylation was observed in HPV16-negative OPSCC patients who relapsed within 24 months, thus indicating the overall level of genomic DNA methylation may have an impact on early OPSCC relapse risk. Despite these promising initial data, the influence of LINE1 methylation levels on OPSCC survival is not yet well defined. We retrospectively reviewed a cohort of 156 patients with stage III–IVB (AJCC TNM 7th Ed.) OPSCC. Forty patients were diagnosed and treated at Treviso Regional Hospital, and 116 at National Cancer Institute of Aviano and/or Pordenone Hospital. All patients were managed with curative intent with elective radiotherapy ± chemotherapy or surgery ± adjuvant (chemo)radiotherapy, in accordance with current clinical practice. Genomic DNA was extracted from OPSCC formalin-fixed paraffin-embedded tissues. The quantification of HPV16 DNA was performed by real-time quantitative PCR by using specific primers for the amplification of a region spanning the E6 genes of the HPV16 genome, whereas the methylation status of LINE1 repetitive sequences was evaluated by real-time quantitative Methylation-Specific PCR. The impact of genome-wide methylation patterns on progression-free survival (PFS) and overall survival (OS) was assessed using Kaplan-Meier analyses. Optimal cut-points for LINE-1 were search through a recursive algorithm which estimates the predictive value for PFS (Harrell's c-index) for each possible couple of LINE-1 values; optimal cut-points were defined as those which maximized Harrell's c-index. Multivariate hazard risk (HR) and corresponding confidence intervals (CI) were calculated according to Cox proportional hazard model adjusting for gender, age, TNM stage, and HPV status.The median follow up was 30 months (interquartile range: 17-72 months) Considering all cases, PFS and OS were respectively 64.6% and 71.8% at 2 years, and 49.5% and 53.7% at 5 years. HPV DNA prevalence was 28.8% (45/156). Compared to HPV-negative patients, HPV-positive ones had a better outcome in terms of PFS at 2 (81.0% vs. 58.2%) and 5 years (70.9% vs 41.6%; p=0.003), as well as in terms of OS (5-year OS: 74.1 vs. 45.9%, respectively; p=0.003). LINE-1 methylation level was significantly higher in HPV-positive OPSCC patients than in HPV-negative ones (median, 66.9% and 48.7% respectively; p<0.001). Three patterns of LINE-1 methylation status were indentified according to PFS: high ≥55%, medium 35-54%, low <35%. The same cut-points were identified from the analysis on OS. Analyzing all patients, PFS at 2 years was 75.9% in the high methylation group, 62.0% in the intermediate group, and 41.6% in the low methylation group (p≤0.001). Compared to LINE-1≥55%, multivariate HR were 1.66 (95% CI: 0.92-2.99) for LINE-1 35-54% and 2.84 (95% CI: 1.51-5.37) for LINE-1<35%. Moreover, OS at 2 and 5 years was significantly better in the high methylation group (p<0.001), with HRs of death similar to those for PFS. It is worth noting that the level of LINE-1 remained a prognostic factor for both PFS (p= 0.004) and of OS (p=0.011) when we restricted the analysis to HPV-negative patients. Among these patients, the multivariate HRs for LINE-1<35% were 2.87 (95% CI: 1.49-5.52) for PFS and 2.86 (1.43-5.74) for OS. In HPV-positive group, respect to patients with LINE-1 <55%, cases with a LINE-1≥55% have had better trend in terms of PFS and OS, but this difference was not statistically significant (p=0.112; p= 0.113), mainly due to small sample size. Between HPV-positive patients, only one had a methylation of LINE-1 < 35%. LINE-1 methylation has been identified as a molecular marker of prognosis for stage III-IV OPSCC patients, becoming a promising biomarker to be integrated in current prognostic factors (e.g., stage, HPV status, tobacco smoking) to refine the comprehensive clinical management of OPSCC. This is of particular clinical relevance for HPV-positive OPSCC patients, since this marker may help in indentify the subset of these patients with bad prognosis. However, further validation in a prospective study is needed for its application in daily clinical practice.
2022-07-14 | E-MTAB-11152 | biostudies-arrayexpress
Project description:Nowadays, risk stratification for oropharyngeal squamous cell carcinoma (OPSCC) is based on HPV status, tobacco smoking, and tumor stage. Although HPV positivity represents a strong prognostic factor for both reduced risk of relapse, and improved survival, there is a subset of HPV-positive OPSCC patients who still experience poor outcomes. Furthermore, HPV-negative OPSCC patients, who have an even higher risk of relapse within two years from the end of the treatment, are still lacking suitable prognostic biomarkers for clinical outcome. In this scenario, inclusion of new biomarkers that differentiate OPSCC patients with a diverse prognosis is urgently needed. Since genes encoding for epigenetic regulators have been frequently found mutated in several tumors, including OPSCC, it is expected that epigenetic changes may play a major role in OPSCC pathogenesis and response to therapy. Consistently, HPV oncoproteins have been also demonstrated to impact on epigenetic pattern by interacting with different epigenetic regulators, thus affecting the chromatin landscape of OPSCC HPV-positive cells. Along this line, we have recently demonstrated the methylation levels of the “Long interspersed nucleotide element-1” (LINE-1) repetitive elements, a widely accepted surrogate of overall genomic DNA methylation content, was different between HPV16-positive and -negative OPSCC patients. In particular, the lowest level of LINE-1 element methylation was observed in HPV16-negative OPSCC patients who relapsed within 24 months, thus indicating the overall level of genomic DNA methylation may have an impact on early OPSCC relapse risk. Despite these promising initial data, the influence of LINE1 methylation levels on OPSCC survival is not yet well defined. We retrospectively reviewed a cohort of 156 patients with stage III–IVB (AJCC TNM 7th Ed.) OPSCC. Forty patients were diagnosed and treated at Treviso Regional Hospital, and 116 at National Cancer Institute of Aviano and/or Pordenone Hospital. All patients were managed with curative intent with elective radiotherapy ± chemotherapy or surgery ± adjuvant (chemo)radiotherapy, in accordance with current clinical practice. Genomic DNA was extracted from OPSCC formalin-fixed paraffin-embedded tissues. The quantification of HPV16 DNA was performed by real-time quantitative PCR by using specific primers for the amplification of a region spanning the E6 genes of the HPV16 genome, whereas the methylation status of LINE1 repetitive sequences was evaluated by real-time quantitative Methylation-Specific PCR. The impact of genome-wide methylation patterns on progression-free survival (PFS) and overall survival (OS) was assessed using Kaplan-Meier analyses. Optimal cut-points for LINE-1 were search through a recursive algorithm which estimates the predictive value for PFS (Harrell's c-index) for each possible couple of LINE-1 values; optimal cut-points were defined as those which maximized Harrell's c-index. Multivariate hazard risk (HR) and corresponding confidence intervals (CI) were calculated according to Cox proportional hazard model adjusting for gender, age, TNM stage, and HPV status.The median follow up was 30 months (interquartile range: 17-72 months) Considering all cases, PFS and OS were respectively 64.6% and 71.8% at 2 years, and 49.5% and 53.7% at 5 years. HPV DNA prevalence was 28.8% (45/156). Compared to HPV-negative patients, HPV-positive ones had a better outcome in terms of PFS at 2 (81.0% vs. 58.2%) and 5 years (70.9% vs 41.6%; p=0.003), as well as in terms of OS (5-year OS: 74.1 vs. 45.9%, respectively; p=0.003). LINE-1 methylation level was significantly higher in HPV-positive OPSCC patients than in HPV-negative ones (median, 66.9% and 48.7% respectively; p<0.001). Three patterns of LINE-1 methylation status were indentified according to PFS: high ≥55%, medium 35-54%, low <35%. The same cut-points were identified from the analysis on OS. Analyzing all patients, PFS at 2 years was 75.9% in the high methylation group, 62.0% in the intermediate group, and 41.6% in the low methylation group (p≤0.001). Compared to LINE-1≥55%, multivariate HR were 1.66 (95% CI: 0.92-2.99) for LINE-1 35-54% and 2.84 (95% CI: 1.51-5.37) for LINE-1<35%. Moreover, OS at 2 and 5 years was significantly better in the high methylation group (p<0.001), with HRs of death similar to those for PFS. It is worth noting that the level of LINE-1 remained a prognostic factor for both PFS (p= 0.004) and of OS (p=0.011) when we restricted the analysis to HPV-negative patients. Among these patients, the multivariate HRs for LINE-1<35% were 2.87 (95% CI: 1.49-5.52) for PFS and 2.86 (1.43-5.74) for OS. In HPV-positive group, respect to patients with LINE-1 <55%, cases with a LINE-1≥55% have had better trend in terms of PFS and OS, but this difference was not statistically significant (p=0.112; p= 0.113), mainly due to small sample size. Between HPV-positive patients, only one had a methylation of LINE-1 < 35%. LINE-1 methylation has been identified as a molecular marker of prognosis for stage III-IV OPSCC patients, becoming a promising biomarker to be integrated in current prognostic factors (e.g., stage, HPV status, tobacco smoking) to refine the comprehensive clinical management of OPSCC. This is of particular clinical relevance for HPV-positive OPSCC patients, since this marker may help in indentify the subset of these patients with bad prognosis. However, further validation in a prospective study is needed for its application in daily clinical practice.
2023-02-21 | E-MTAB-12032 | biostudies-arrayexpress
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