Brush swab as a noninvasive surrogate for tissue biopsies in epigenomic profiling of oral cancer.

Autor: Viet CT; Department of Oral and Maxillofacial Surgery, Loma Linda University School of Dentistry, Loma Linda, CA, USA. cviet@llu.edu., Zhang X; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; VA Connecticut Healthcare System, West Haven, CT, USA., Xu K; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; VA Connecticut Healthcare System, West Haven, CT, USA., Yu G; New York University Rory Meyers College of Nursing, New York, NY, USA., Asam K; Department of Oral and Maxillofacial Surgery, New York University College of Dentistry, New York, NY, USA.; Bluestone Center for Clinical Research, New York University College of Dentistry, New York, NY, USA., Thomas CM; Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA., Callahan NF; Department of Oral and Maxillofacial Surgery, University of Illinois Chicago, College of Dentistry, Chicago, IL, USA., Doan C; Department of Oral and Maxillofacial Surgery, Loma Linda University School of Dentistry, Loma Linda, CA, USA., Walker PC; Department of Otolaryngology, Loma Linda University School of Medicine, Loma Linda, CA, USA., Nguyen K; Department of Otolaryngology, Loma Linda University School of Medicine, Loma Linda, CA, USA., Kidd SC; Department of Otolaryngology, Loma Linda University School of Medicine, Loma Linda, CA, USA., Lee SC; Department of Otolaryngology, Loma Linda University School of Medicine, Loma Linda, CA, USA., Grandhi A; Department of Oral and Maxillofacial Surgery, Loma Linda University School of Dentistry, Loma Linda, CA, USA., Allen CT; Section on Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH), Bethesda, MD, USA., Young S; Department of Oral, Head and Neck Oncology and Microvascular Reconstructive Surgery, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, USA., Melville JC; Department of Oral, Head and Neck Oncology and Microvascular Reconstructive Surgery, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, USA., Shum JW; Department of Oral, Head and Neck Oncology and Microvascular Reconstructive Surgery, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, USA., Viet DT; Rocky Vista University, Ivins, UT, USA., Herford AS; Department of Oral and Maxillofacial Surgery, Loma Linda University School of Dentistry, Loma Linda, CA, USA., Roden DF; Department of Otolaryngology, Rutgers New Jersey Medical School, Newark, NJ, USA., Gonzalez ML; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA., Zhong JF; Department of Basic Sciences, Loma Linda University, School of Medicine, Loma Linda, CA, USA., Aouizerat BE; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; VA Connecticut Healthcare System, West Haven, CT, USA.; New York University Rory Meyers College of Nursing, New York, NY, USA.
Jazyk: angličtina
Zdroj: Biomarker research [Biomark Res] 2021 Dec 20; Vol. 9 (1), pp. 90. Date of Electronic Publication: 2021 Dec 20.
DOI: 10.1186/s40364-021-00349-x
Abstrakt: Background: Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients.
Methods: Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies.
Results: There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11).
Conclusions: Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.
(© 2021. The Author(s).)
Databáze: MEDLINE
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