Plasma cell-free DNA methylome profiling in pre- and post-surgery oral cavity squamous cell carcinoma

Krupal B Patel; Tapan A Padhya; Jinyong Huang; Juan C Hernandez-Prera; Tingyi Li; Christine H Chung; Liang Wang; Xuefeng Wang

doi:10.1002/mc.23501

Plasma cell-free DNA methylome profiling in pre- and post-surgery oral cavity squamous cell carcinoma

Mol Carcinog. 2023 Apr;62(4):493-502. doi: 10.1002/mc.23501. Epub 2023 Jan 13.

Authors

Krupal B Patel¹, Tapan A Padhya², Jinyong Huang³, Juan C Hernandez-Prera⁴, Tingyi Li⁵, Christine H Chung¹, Liang Wang³, Xuefeng Wang^{5

6}

Affiliations

¹ Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
² Otolaryngology-Head and Neck Surgery, University of South Florida Morsani College of Medicine, Tampa, USA.
³ Department of Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
⁴ Department of Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
⁵ Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
⁶ Moffitt Cancer Center Immuno-Oncology Program, Tampa, Florida, USA.

Abstract

Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous disease that involves multiple anatomic sites, is a leading cause of cancer-related mortality worldwide. Although the utility of noninvasive biomarkers based on circulating cell-free DNA (cfDNA) methylation profiling has been widely recognized, limited studies have been reported so far regarding the dynamics of cfDNA methylome in oral cavity squamous cell carcinoma (OCSCC). It is hypothesized in this study that comparison of methylation profiles in pre- and postsurgery plasma samples will reveal OCSCC-specific prognostic and diagnostic biomarkers. As a strategy to further prioritize tumor-specific targets, top differential methylated regions (DMRs) were called by reanalyzing methylation data from paired tumor and normal tissue collected in the the cancer genome atlas head-neck squamous cell carcinoma (TCGA) head and neck cancer cohort. Matched plasma samples from eight patients with OCSCC were collected at Moffitt Cancer Center before and after surgical resection. Plasma-derived cfDNA was analyzed by cfMBD-seq, which is a high-sensitive methylation profiling assay. Differential methylation analysis was then performed based on the matched samples profiled. In the top 200 HNSCC-specific DMRs detected based on the TCGA data set, a total of 23 regions reached significance in the plasma-based DMR test. The top five validated DMR regions (ranked by the significance in the plasma study) are located in the promoter regions of genes PENK, NXPH1, ZIK1, TBXT, and CDO1, respectively. The genome-wide cfDNA DMR analysis further highlighted candidate biomarkers located in genes SFRP4, SOX1, IRF4, and PCDH17. The prognostic relevance of candidate genes was confirmed by survival analysis using the TCGA data. This study supports the utility of cfDNA-based methylome profiling as a promising noninvasive biomarker source for OCSCC and HNSCC.

Keywords: cell-free DNA; head and neck cancer; methylation biomarkers; oral cavity squamous cell carcinoma; plasma.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Carcinoma, Squamous Cell* / genetics
Carcinoma, Squamous Cell* / surgery
Cell-Free Nucleic Acids* / genetics
DNA Methylation
Epigenome
Head and Neck Neoplasms* / genetics
Head and Neck Neoplasms* / surgery
Humans
Mouth Neoplasms* / genetics
Mouth Neoplasms* / surgery
Squamous Cell Carcinoma of Head and Neck / genetics
Squamous Cell Carcinoma of Head and Neck / surgery

Substances

Biomarkers, Tumor
Cell-Free Nucleic Acids

Abstract

Publication types

MeSH terms

Substances

Grants and funding