title: Outlier Analysis Defines Zinc Finger Gene Family DNA Methylation in Tumors and Saliva of Head and Neck Cancer Patients.
abstract: Head and Neck Squamous Cell Carcinoma (HNSCC) is the fifth most common cancer, annually affecting over half a million people worldwide. Presently, there are no accepted biomarkers for clinical detection and surveillance of HNSCC. In this work, a comprehensive genome-wide analysis of epigenetic alterations in primary HNSCC tumors was employed in conjunction with cancer-specific outlier statistics to define novel biomarker genes which are differentially methylated in HNSCC. The 37 identified biomarker candidates were top-scoring outlier genes with prominent differential methylation in tumors, but with no signal in normal tissues. These putative candidates were validated in independent HNSCC cohorts from our institution and TCGA (The Cancer Genome Atlas). Using the top candidates, ZNF14, ZNF160, and ZNF420, an assay was developed for detection of HNSCC cancer in primary tissue and saliva samples with 100% specificity when compared to normal control samples. Given the high detection specificity, the analysis of ZNF DNA methylation in combination with other DNA methylation biomarkers may be useful in the clinical setting for HNSCC detection and surveillance, particularly in high-risk patients. Several additional candidates identified through this work can be further investigated toward future development of a multi-gene panel of biomarkers for the surveillance and detection of HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Daria A
authors.initials: DA
authors.lastname: Gaykalova
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Department of Urology, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Rajita
authors.initials: R
authors.lastname: Vatapalli
authors.affiliation: Division of Oncology Biostatistics, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Department of Statistics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Division of Oncology Biostatistics, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Tsai
authors.affiliation: Division of Oncology Biostatistics, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|University of Virginia, Department of Pathology, Charlottesville, Virginia, United States of America.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Hennessey
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Theresa
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Marietta
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Zubair
authors.initials: Z
authors.lastname: Khan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Zaboli
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Koch
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Tanbir
authors.initials: T
authors.lastname: Khan
authors.affiliation: Division of Oncology Biostatistics, Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Department of Mathematics and Statistics, The College of New Jersey, Ewing, New Jersey, United States of America.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ochs
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.|Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland, United States of America.|Division of Otolaryngology / Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000821:virology; D027383:Papillomaviridae; D012097:Repressor Proteins / Q000235:genetics; D012463:Saliva / Q000378:metabolism; D012680:Sensitivity and Specificity; D016335:Zinc Fingers
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C540923:ZNF420 protein, human; C545341:zinc finger protein 160, human