Abstract
BackgroundSquamous 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.ResultsPITX2 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).MethodsQuantitative, 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).ConclusionsPITX2 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.
Highlights
Cancer of the head and neck region is a frequent and worldwide health burden with 61.760 estimated new cases and 13.190 estimated deaths in the United States for 2016 alone [1]
The PITX2 methylation quantitative methylation-specific real-time polymerase chain reaction (PCR) assay used in the presented study has previously been described in two studies [43, 44]
FFPE samples from 399 patients with HNSCC were analyzed for PITX2 and PITX2 and an adjacent long non-coding RNAs (lncRNA) (PANCR) methylation
Summary
Cancer of the head and neck region is a frequent and worldwide health burden with 61.760 estimated new cases and 13.190 estimated deaths in the United States for 2016 alone [1]. More than 90% of these tumors are squamous cell carcinomas (HNSCC) occurring in the oral and nasal cavity, pharynx, and larynx [2]. Tobacco smoking and alcohol consumption are well known carcinogenic risk factors, during the past two decades human papilloma virus (HPV) infections have been related to oropharyngeal carcinomas. HPV-related tumors www.impactjournals.com/oncotarget are a distinct entity that is associated with an overall better prognosis [3,4,5], and an etiological link between infection with high risk HPV serotypes 16 and 18 and the development of oropharyngeal tumors is well documented [6]. 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. The methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients
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