Karolina E Kaczor-Urbanowicz1,2, Harsh M Trivedi3, Patricia O Lima1,4, Paulo M Camargo5, William V Giannobile6, Tristan R Grogan7, Frederico O Gleber-Netto8, Yair Whiteman9, Feng Li1, Hyo Jung Lee10, Karan Dharia11, Katri Aro1, Carmen Martin Carreras-Presas12, Saarah Amuthan11, Manjiri Vartak11, David Akin1, Hiba Al-Adbullah11, Kanika Bembey11, Perry R Klokkevold5, David Elashoff7, Virginia M Barnes13, Rose Richter13, William DeVizio13, James G Masters3, David T W Wong1. 1. UCLA School of Dentistry, Center for Oral/Head & Neck Oncology Research, University of California at Los Angeles, Los Angeles, California. 2. Section of Orthodontics, UCLA School of Dentistry, University of California at Los Angeles, Los Angeles, California. 3. Early Research Oral Care, Colgate Palmolive Co., Piscataway, New Jersey. 4. Department of Physiological Sciences, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil. 5. Section of Periodontics, UCLA School of Dentistry, University of California at Los Angeles, Los Angeles, California. 6. Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan. 7. Department of Biostatistics, University of California at Los Angeles, Los Angeles, California. 8. Medical Genomics Laboratory, Centro Internacional de Pesquisa e Ensino (CIPE), AC Camargo Cancer Center, São Paulo, Brazil. 9. UCLA School of Dentistry, Center for Esthetic Dentistry, University of California at Los Angeles, Los Angeles, California. 10. Section of Dentistry, Department of Periodontology, Seoul National University Bundang Hospital, Seoul, Korea. 11. UCLA School of Dentistry, University of California at Los Angeles, Los Angeles, California. 12. Faculty of Biomedical Sciences, Adult's Dentistry Department, Universidad Europea de Madrid, Madrid, Spain. 13. Clinical Research Oral Care, Colgate Palmolive Co., Piscataway, New Jersey.
Abstract
AIM: This study tests the hypothesis that salivary extracellular RNA (exRNA) biomarkers can be developed for gingivitis detection and monitoring disease regression. MATERIALS AND METHODS: Salivary exRNA biomarker candidates were developed from a total of 100 gingivitis and non-gingivitis individuals using Affymetrix's expression microarrays. The top 10 differentially expressed exRNAs were tested in a clinical cohort to determine whether the discovered salivary exRNA markers for gingivitis were associated with clinical gingivitis and disease regression. For this purpose, unstimulated saliva was collected from 30 randomly selected gingivitis subjects, the gingival and plaque indexes scores were taken at baseline, 3 and 6 weeks and salivary exRNAs were assayed by means of reverse transcription quantitative polymerase chain reaction. RESULTS: Eight salivary exRNA biomarkers developed for gingivitis were statistically significantly changed over time, consistent with disease regression. A panel of four salivary exRNAs [SPRR1A, lnc-TET3-2:1, FAM25A, CRCT1] can detect gingivitis with a clinical performance of 0.91 area under the curve, with 71% sensitivity and 100% specificity. CONCLUSIONS: The clinical values of the developed salivary exRNA biomarkers are associated with gingivitis regression. They offer strong potential to be advanced for definitive validation and clinical laboratory development test.
AIM: This study tests the hypothesis that salivary extracellular RNA (exRNA) biomarkers can be developed for gingivitis detection and monitoring disease regression. MATERIALS AND METHODS: Salivary exRNA biomarker candidates were developed from a total of 100 gingivitis and non-gingivitis individuals using Affymetrix's expression microarrays. The top 10 differentially expressed exRNAs were tested in a clinical cohort to determine whether the discovered salivary exRNA markers for gingivitis were associated with clinicalgingivitis and disease regression. For this purpose, unstimulated saliva was collected from 30 randomly selected gingivitis subjects, the gingival and plaque indexes scores were taken at baseline, 3 and 6 weeks and salivary exRNAs were assayed by means of reverse transcription quantitative polymerase chain reaction. RESULTS: Eight salivary exRNA biomarkers developed for gingivitis were statistically significantly changed over time, consistent with disease regression. A panel of four salivary exRNAs [SPRR1A, lnc-TET3-2:1, FAM25A, CRCT1] can detect gingivitis with a clinical performance of 0.91 area under the curve, with 71% sensitivity and 100% specificity. CONCLUSIONS: The clinical values of the developed salivary exRNA biomarkers are associated with gingivitis regression. They offer strong potential to be advanced for definitive validation and clinical laboratory development test.
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