title: microRNA from brush biopsy to characterize oral squamous cell carcinoma epithelium.
abstract: Few cancers are diagnosed based on RNA expression signatures. Oral squamous cell carcinoma (OSCC) is no exception; it is currently diagnosed by scalpel biopsy followed by histopathology. This study sought to identify oral tumor epithelial microRNA (miRNA) expression changes to determine if these changes could be used to diagnose the disease noninvasively. Analysis of miRNA profiles from surgically obtained OSCC tissue, collected under highly standardized conditions for The Cancer Genome Atlas, was done to determine the potential accuracy in differentiating tumor from normal mucosal tissue. Even when using small 20 subject datasets, classification based on miRNA was 90 to 100% accurate. To develop a noninvasive classifier for OSSC, analysis of brush biopsy miRNA was done and showed 87% accuracy in differentiating tumor from normal epithelium when using RT-qPCR or miRNAseq to measure miRNAs. An extensive overlap was seen in differentially expressed miRNAs in oral squamous cell carcinoma epithelium obtained using brush biopsy and those reported in saliva and serum of oral squamous cell carcinoma patients in several studies. This suggested that nonselective release of these miRNAs into body fluids from tumor epithelium was largely responsible for the changes in levels in these fluids seen with this disease. Using a variation in mirRPath we identified the KEGG pathway of neurotrophin signaling as a target of these miRNAs disregulated in tumor epithelium. This highlights the utility of brush biopsy of oral mucosa to allow simple acquisition of cancer relevant miRNA information from tumor epithelium.
authors.affiliation: Department of Oral Medicine and Oral Diagnostics, Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 801 South Paulina Street, Chicago, Illinois, 60610.|Arphion Ltd, 2242 W Harrison Street, Chicago, Illinois, 60612.
authors.forename: Yalu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Illinois at Chicago, 801 South Paulina Street, Chicago, Illinois, 60610.
authors.forename: Antonia
authors.initials: A
authors.lastname: Kolokythas
authors.affiliation: Department of Oral Medicine and Oral Diagnostics, Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 801 South Paulina Street, Chicago, Illinois, 60610.
authors.forename: Joel L
authors.initials: JL
authors.lastname: Schwartz
authors.affiliation: Cancer Dentistry Program, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Epstein
authors.affiliation: Department of Oral Medicine and Oral Diagnostics, Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 801 South Paulina Street, Chicago, Illinois, 60610.
authors.forename: Guy R
authors.initials: GR
authors.lastname: Adami
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: Brush biopsy; head and neck cancer; miRNA; the Cancer Genome Atlas