Novel DNA methylation targets in oral rinse samples predict survival of patients with oral squamous cell carcinoma

Abstract

Objectives The objective of this study was to identify novel survival-associated biomarkers in oral rinse samples collected from patients with oral squamous cell carcinoma (OSCC). Materials & Methods We screened for putative survival-associated markers using publicly available methylation array data from 88 OSCC tumors. Cox models were then fit to methylation array data restricted to these putative loci in oral rinse samples of 82 OSCC patients from greater Boston. Pyrosequencing assays were designed for each locus that replicated in the oral rinse samples and applied to a validation set of oral rinse samples from another 61 OSCC patients. Results We identified 7 survival-associated methylation markers in oral rinse samples from OSCC patients, and have validated one, located in the body of GABBR1, by pyrosequencing. Conclusion The 7 CpG loci identified through this study represent novel prognostic biomarkers for patients with OSCC that can be detected using a non-invasive oral rinse collection technique.

Stability of methylation markers in head and neck squamous cell carcinoma

“…CD1A methylation has not been previously studied in HNSCC, however, significant hypermethylation of CD1B , CD1C , CD1DI , and CD1E has been found in HPV‐positive HNSCC tumors compared with HPV‐negative tumors . Deleted in colorectal carcinoma ( DCC ) and CCNA1 was previously found to be hypermethylated in HNSCC and were chosen for its role as a tumor suppressor and involvement with HPV . Previous literature on the importance of these genes in HNSCC highlights their potential clinical relevance.…”

Hypermethylated ZNF582 and PAX1 genes in mouth rinse samples as biomarkers for oral dysplasia and oral cancer detection

“…Moreover, biopsy is an invasive procedure that is easy to be refused by the patients with suspicious oral potentially malignant disorder lesions. Several studies have attempted to detect OSCC using aberrant DNA methylation in samples obtained from mouth rinse or saliva . However, the reported sensitivity and specificity of using only 1 methylated gene for oral cancer detection are not high enough to justify its use as an effective oral cancer screening method .…”

“…Several studies have attempted to detect OSCC using aberrant DNA methylation in samples obtained from mouth rinse or saliva. [10][11][12][13][14] However, the reported sensitivity and specificity of using only 1 methylated gene for oral cancer detection are not high enough to justify its use as an effective oral cancer screening method. [10][11][12][13][14] This study showed that the ZNF582 m or PAX1 m test using oral epithelial cells collected by the mouth rinse method had relatively high discriminatory ability for screening oral dysplasia and oral cancer, as evidenced by relatively high AUC values and ORs.…”

“…Using oral scraping, mouth rinse, saliva, and vital staining to screen oral potentially malignant disorders and OSCC lesions has been proposed and studied for a long time . However, the results from these studies varied in some degree depending on the quality of oral epithelial cells collected and biomarkers used.…”

“…Using oral scraping, mouth rinse, saliva, and vital staining to screen oral potentially malignant disorders and OSCC lesions has been proposed and studied for a long time. [8][9][10][11][12][13][14][15][16] However, the results from these studies varied in some degree depending on the quality of oral epithelial cells collected and biomarkers used. For the oral scraping method, an experienced practitioner is the key factor to collect the proper oral lesional epithelial cells for tests.…”