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Transcriptomic profiles and their correlations in saliva and gingival tissue biopsy samples from periodontitis and healthy patients

  • Jeon, Yoon-Sun (Department of Periodontology, Research Institute of Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Cha, Jae-Kook (Department of Periodontology, Research Institute of Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Choi, Seong-Ho (Department of Periodontology, Research Institute of Periodontal Regeneration, Yonsei University College of Dentistry) ;
  • Lee, Ji-Hyun (Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine) ;
  • Lee, Jung-Seok (Department of Periodontology, Research Institute of Periodontal Regeneration, Yonsei University College of Dentistry)
  • Received : 2019.12.09
  • Accepted : 2020.08.17
  • Published : 2020.10.30

Abstract

Purpose: This study was conducted to analyze specific RNA expression profiles in gingival tissue and saliva samples in periodontitis patients and healthy individuals, and to determine their correlations in light of the potential use of microarray-based analyses of saliva samples as a periodontal monitoring tool. Methods: Gingival tissue biopsies and saliva samples from 22 patients (12 with severe periodontitis and 10 with a healthy periodontium) were analyzed using transcriptomic microarray analysis. Differential gene expression was assessed, and pathway and clustering analyses were conducted for the samples. The correlations between the results for the gingival tissue and saliva samples were analyzed at both the gene and pathway levels. Results: There were 621 differentially expressed genes (DEGs; 320 upregulated and 301 downregulated) in the gingival tissue samples of the periodontitis group, and 154 DEGs (44 upregulated and 110 downregulated) in the saliva samples. Nine of these genes overlapped between the sample types. The periodontitis patients formed a distinct cluster group based on gene expression profiles for both the tissue and saliva samples. Database for Annotation, Visualization and Integrated Discovery analysis revealed 159 enriched pathways from the tissue samples of the periodontitis patients, as well as 110 enriched pathways In the saliva samples. Thirty-four pathways overlapped between the sample types. Conclusions: The present results indicate the possibility of using the salivary transcriptome to distinguish periodontitis patients from healthy individuals. Further work is required to enhance the extraction of available RNA from saliva samples.

Keywords

References

  1. Al-Yahfoufi Z, Mombelli A, Wicki A, Lang NP. The effect of plaque control in subjects with shallow pockets and high prevalence of periodontal pathogens. J Clin Periodontol 1995;22:78-84. https://doi.org/10.1111/j.1600-051X.1995.tb01774.x
  2. Trombelli L, Tatakis DN, Scapoli C, Bottega S, Orlandini E, Tosi M. Modulation of clinical expression of plaque-induced gingivitis. II. Identification of "high-responder" and "low-responder" subjects. J Clin Periodontol 2004;31:239-52. https://doi.org/10.1111/j.1600-051x.2004.00478.x
  3. Loe H, Anerud A, Boysen H, Morrison E. Natural history of periodontal disease in man. Rapid, moderate and no loss of attachment in Sri Lankan laborers 14 to 46 years of age. J Clin Periodontol 1986;13:431-45. https://doi.org/10.1111/j.1600-051X.1986.tb01487.x
  4. Halazonetis TD, Haffajee AD, Socransky SS. Relationship of clinical parameters to attachment loss in subsets of subjects with destructive periodontal diseases. J Clin Periodontol 1989;16:563-8. https://doi.org/10.1111/j.1600-051X.1989.tb02138.x
  5. Goncalves LDR, Soares MR, Nogueira FCS, Garcia C, Camisasca DR, Domont G, et al. Comparative proteomic analysis of whole saliva from chronic periodontitis patients. J Proteomics 2010;73:1334-41. https://doi.org/10.1016/j.jprot.2010.02.018
  6. Demmer RT, Behle JH, Wolf DL, Handfield M, Kebschull M, Celenti R, et al. Transcriptomes in healthy and diseased gingival tissues. J Periodontol 2008;79:2112-24. https://doi.org/10.1902/jop.2008.080139
  7. Jonsson D, Ramberg P, Demmer RT, Kebschull M, Dahlen G, Papapanou PN. Gingival tissue transcriptomes in experimental gingivitis. J Clin Periodontol 2011;38:599-611. https://doi.org/10.1111/j.1600-051X.2011.01719.x
  8. Kebschull M, Guarnieri P, Demmer RT, Boulesteix AL, Pavlidis P, Papapanou PN. Molecular differences between chronic and aggressive periodontitis. J Dent Res 2013;92:1081-8. https://doi.org/10.1177/0022034513506011
  9. Taiete T, Casarin RCV, Ruiz KGS, Nociti FH Jr, Sallum EA, Casati MZ. Transcriptome of healthy gingival tissue from edentulous sites in patients with a history of generalized aggressive periodontitis. J Periodontol 2018;89:93-104.
  10. Offenbacher S, Barros SP, Paquette DW, Winston JL, Biesbrock AR, Thomason RG, et al. Gingival transcriptome patterns during induction and resolution of experimental gingivitis in humans. J Periodontol 2009;80:1963-82. https://doi.org/10.1902/jop.2009.080645
  11. Davanian H, Stranneheim H, Bage T, Lagervall M, Jansson L, Lundeberg J, et al. Gene expression profiles in paired gingival biopsies from periodontitis-affected and healthy tissues revealed by massively parallel sequencing. PLoS One 2012;7:e46440. https://doi.org/10.1371/journal.pone.0046440
  12. Kaczor-Urbanowicz KE, Martin Carreras-Presas C, Aro K, Tu M, Garcia-Godoy F, Wong DT. Saliva diagnostics - current views and directions. Exp Biol Med (Maywood) 2017;242:459-72. https://doi.org/10.1177/1535370216681550
  13. Zhang L, Henson BS, Camargo PM, Wong DT. The clinical value of salivary biomarkers for periodontal disease. Periodontol 2000 2009;51:25-37. https://doi.org/10.1111/j.1600-0757.2009.00315.x
  14. Li Y, Zhou X, St John MAR, Wong DTW. RNA profiling of cell-free saliva using microarray technology. J Dent Res 2004;83:199-203. https://doi.org/10.1177/154405910408300303
  15. Hu S, Wang J, Meijer J, Ieong S, Xie Y, Yu T, et al. Salivary proteomic and genomic biomarkers for primary Sjogren's syndrome. Arthritis Rheum 2007;56:3588-600. https://doi.org/10.1002/art.22954
  16. Li Y, St John MA, Zhou X, Kim Y, Sinha U, Jordan RC, et al. Salivary transcriptome diagnostics for oral cancer detection. Clin Cancer Res 2004;10:8442-50. https://doi.org/10.1158/1078-0432.CCR-04-1167
  17. Javaid MA, Ahmed AS, Durand R, Tran SD. Saliva as a diagnostic tool for oral and systemic diseases. J Oral Biol Craniofac Res 2016;6:66-75.
  18. Navazesh M. Methods for collecting saliva. Ann N Y Acad Sci 1993;694:72-7. https://doi.org/10.1111/j.1749-6632.1993.tb18343.x
  19. Huang W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009;37:1-13. https://doi.org/10.1093/nar/gkn923
  20. Becker ST, Beck-Broichsitter BE, Graetz C, Dorfer CE, Wiltfang J, Hasler R. Peri-implantitis versus periodontitis: functional differences indicated by transcriptome profiling. Clin Implant Dent Relat Res 2014;16:401-11. https://doi.org/10.1111/cid.12001
  21. Zhang L, Farrell JJ, Zhou H, Elashoff D, Akin D, Park NH, et al. Salivary transcriptomic biomarkers for detection of resectable pancreatic cancer. Gastroenterology 2010;138:949-957.e1-7. https://doi.org/10.1053/j.gastro.2009.11.010
  22. Hjelmervik TOR, Petersen K, Jonassen I, Jonsson R, Bolstad AI. Gene expression profiling of minor salivary glands clearly distinguishes primary Sjogren's syndrome patients from healthy control subjects. Arthritis Rheum 2005;52:1534-44. https://doi.org/10.1002/art.21006
  23. Guzeldemir-Akcakanat E, Sunnetci-Akkoyunlu D, Orucguney B, Cine N, Kan B, Yilmaz EB, et al. Gene-expression profiles in generalized aggressive periodontitis: a gene network-based microarray analysis. J Periodontol 2016;87:58-65. https://doi.org/10.1902/jop.2015.150175
  24. Guo X, Wang Y, Wang C, Chen J. Identification of several hub-genes associated with periodontitis using integrated microarray analysis. Mol Med Rep 2015;11:2541-7. https://doi.org/10.3892/mmr.2014.3031
  25. Zhang B, Lin T, He H. Comparative analysis of blood and saliva expression profiles in chronic and refractory periodontitis patients. BMC Oral Health 2015;15:166. https://doi.org/10.1186/s12903-015-0150-3
  26. Giannobile WV, Beikler T, Kinney JS, Ramseier CA, Morelli T, Wong DT. Saliva as a diagnostic tool for periodontal disease: current state and future directions. Periodontol 2000 2009;50:52-64. https://doi.org/10.1111/j.1600-0757.2008.00288.x
  27. Loos BG, Tjoa S. Host-derived diagnostic markers for periodontitis: do they exist in gingival crevice fluid? 2005;39:53-72. https://doi.org/10.1111/j.1600-0757.2005.00129.x
  28. Teng YT, Sodek J, McCulloch CA. Gingival crevicular fluid gelatinase and its relationship to periodontal disease in human subjects. J Periodontal Res 1992;27:544-52. https://doi.org/10.1111/j.1600-0765.1992.tb01830.x
  29. Hidayat MF, Milne T, Cullinan MP, Seymour GJ. Feasibility of the salivary transcriptome as a novel biomarker in determining disease susceptibility. J Periodontal Res 2018;53:369-77. https://doi.org/10.1111/jre.12522
  30. Hasselmann DO, Rappl G, Tilgen W, Reinhold U. Extracellular tyrosinase mRNA within apoptotic bodies is protected from degradation in human serum. Clin Chem 2001;47:1488-9. https://doi.org/10.1093/clinchem/47.8.1488
  31. Park NJ, Yu T, Nabili V, Brinkman BM, Henry S, Wang J, et al. RNAprotect saliva: an optimal room- temperature stabilization reagent for the salivary transcriptome. Clin Chem 2006;52:2303-4. https://doi.org/10.1373/clinchem.2006.075598
  32. Park NJ, Zhou X, Yu T, Brinkman BM, Zimmermann BG, Palanisamy V, et al. Characterization of salivary RNA by cDNA library analysis. Arch Oral Biol 2007;52:30-5. https://doi.org/10.1016/j.archoralbio.2006.08.014
  33. Belstrom D, Damgaard C, Kononen E, Gursoy M, Holmstrup P, Gursoy UK. Salivary cytokine levels in early gingival inflammation. 2017;9:1364101. https://doi.org/10.1080/20002297.2017.1364101
  34. Paula-Silva FWG, Petean IBF, da Silva LAB, Faccioli LH. Dual role of 5-lipoxygenase in osteoclastogenesis in bacterial-induced apical periodontitis. J Endod 2016;42:447-54. https://doi.org/10.1016/j.joen.2015.12.003

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