Dataset Information

PITX2 and PANCR DNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma.

ABSTRACT: BACKGROUND:Squamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients. RESULTS:PITX2 hypermethylation was associated with a better overall survival (hazard ratio, HR = 0.51, 95%CI: 0.35-0.74, p<0.001), while PANCR hypermethylation was significantly associated with an increased risk of death (HR = 1.64, 95%CI: 1.12-2.39, p=0.010). METHODS:Quantitative, methylation-specific real-time PCR assays for PITX2 and PANCR were employed to measure bisulfite-converted DNA from formalin-fixed, paraffin-embedded (FFPE) tissues in a cohort of 399 patients with localized or locally advanced HNSCC who received curative-intent treatment (surgery with optional adjuvant radiochemotherapy or definite radiochemotherapy). CONCLUSIONS:PITX2 and PANCR methylation status were shown to be independent predictors for overall survival in HNSCC patients. Tissue-based methylation testing could therefore potentially be employed to identify patients with a high risk for death who might benefit from a more radical or alternative treatment.

SUBMITTER: Sailer V

PROVIDER: S-EPMC5342781 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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PITX2 and PANCR DNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma.

Sailer Verena V Holmes Emily Eva EE Gevensleben Heidrun H Goltz Diane D Dröge Freya F de Vos Luka L Franzen Alina A Schröck Friederike F Bootz Friedrich F Kristiansen Glen G Schröck Andreas A Dietrich Dimo D

Oncotarget 20161101 46

<h4>Background</h4>Squamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients.<h4>Results</h4> ...[more]

PMID: 27716615

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Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is a common cancer characterized by late diagnosis and poor prognosis. The aim of this study was to identify a novel ferroptosis-related DNA methylation signature as an alternative diagnosis index for patients with HNSCC.MethodsMethylome and transcriptome data of 499 HNSCC patients, including 275 oral squamous cell carcinoma (OSCC) samples, were obtained from The Cancer Genome Atlas (TCGA). An additional independent methylation dataset of 50 OSCC patients from the NCBI Gene Expression Omnibus (GEO) database was used for validation. As an index of ferroptosis activity, the ferroptosis score (FS) of each patient was inferred from the transcriptome data using single-sample gene set enrichment analysis. Univariate, multivariate, and LASSO Cox regression analyses were used to select CpG sites for the construction of a ferroptosis-related DNA methylation signature for diagnosis of patients.ResultsWe initially inferred the FS of each TCGA HNSCC patient and divided the samples into high- and low-FS subgroups. Results showed that the high-FS subgroup displayed poor overall survival. Moreover, 378 differentially methylated CpG sites (DMCs) were identified between the two HNSCC subgroups, with 16 selected to construct a 16-DNA methylation signature for risk prediction in HNSCC patients using the LASSO and multivariate Cox regression models. Relative operating characteristic (ROC) curve analysis showed great predictive efficiency for 1-, 3-, and 5-year HNSCC survival using the 16-DNA methylation signature. Its predictive efficiency was also observed in OSCC patients from the TCGA and GEO databases. In addition, we found that the signature was associated with the fractions of immune types in the tumor immune microenvironment (TIME), suggesting potential interactions between ferroptosis and TIME in HNSCC progression.ConclusionsWe established a novel ferroptosis-related 16-DNA methylation signature that could be applied as an alternative tool to predict prognosis outcome in patients with HNSCC, including OSCC.

Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is a common malignancy that emanates from the lips, mouth, paranasal sinuses, oropharynx, larynx, nasopharynx, and from other pharyngeal cancers. The availability of high-throughput expression data has made it possible to use global gene expression data to analyze the relationship between metabolic-related gene expression and clinical outcomes in HNSCC patients.MethodIn this study, we used RNA sequencing (RNA-seq) data from the cancer genome atlas (TCGA), with validation in the GEO dataset to profile the metabolic microenvironment and define potential biomarkers for metabolic therapy.ResultsWe extracted data for 529 patients and 327 metabolic genes (198 upregulated and 129 downregulated genes) in the TCGA database. Carbonic anhydrase 9 (CA9) and CA6 had the largest logFCs in the upregulated and downregulated genes, respectively. Our Cox regression model data showed 51 prognostic-related genes with lysocardiolipin acyltransferase 1 (LCLAT1) and choline dehydrogenase (CHDH) being associated with the highest risk (HR = 1.144, 95% CI = 1.044 ~ 1.251) and the lowest risk (HR = 0.580, 95% CI = 0.400 ~ 0.839) in HNSCC, respectively. We next used the ROC curve to evaluate whether the differentially expressed metabolic-related genes could serve as early predictors of HNSCC. The findings showed an AUC of 0.745 and 0.618 in the TCGA and GEO analysis, respectively. Besides, the ability for the genes to predict clinicopathological HNSCC status was analyzed and the data showed that the AUC for age, gender, grade, stage, T, M, and N was 0.520, 0.495, 0.568, 0.606, 0.577, 0.476, and 0.673, respectively, in the TCGA dataset. On the other hand, the AUC for age, gender, stage, T, M, N, smoking, and HPV16-pos was 0.599, 0.531, 0.622, 0.606, 0.616, 0.550, 0.614, 0.519, and 0.397, respectively, in the GEO dataset.ConclusionTaken together, our study unearths a novel metabolic gene signature for the prediction of HNSCC prognosis based on the TCGA dataset. Our signature might point out the metabolic microenvironment disorders and provides potential treatment targets and prognostic biomarkers.

Dataset Information

PITX2 and PANCR DNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma.

Publications

PITX2 and PANCR DNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma.

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