Int J Stomatol

Int J Stomatol ›› 2023, Vol. 50 ›› Issue (3): 321-328.doi: 10.7518/gjkq.2023044

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New advances in oral diseases based on salivary metabolomics

Yang Qianjuan1(),Song Zhixin1,Fang Shishu2,Gu Zexu1,Jin Zuolin1,Liu Qian1()   

  1. 1.Dept. of Orthodontics, School of Stomatology, The Air Force Medical University, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Xi’an 710032, China
    2.Dept. of Stomatology, General Hospital of Southern Theater Command of the Chinese People’s Liberation Army, Guangzhou 510010, China
  • Received:2022-11-05 Revised:2023-03-10 Online:2023-05-01 Published:2023-05-16
  • Contact: Qian Liu E-mail:kq1966@126.com;xj6767@163.com
  • Supported by:
    Key Research and Development Program of Shaanxi Province(2021SF-048);Class A Project of 2020 Special Project of the National Clinical Research Center for Oral Diseases(LCA202009)

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Abstract:

Salivary metabolomics is a newly developing subject that investigates the changes of metabolites in orga-nisms qualitatively and quantitatively in order to study the disease and health of organisms with saliva as the research object. Studies in the field of stomatology found some connection issues between saliva metabolites and diverse oral disea-ses. This article reviews the recent progress in oral-disease-related research that uses salivary metabolomics as a research method, including oral squamous cell carcinoma, oral mucosa precancerous lesion (oral lichen planus and oral leukoplakia), recurrent Aphthous ulcer, primary Sjogren syndrome, early childhood caries, periodontitis, chronic periapical inflammation, and root resorption after orthodontics. By summarizing the relevant differential metabolites and signaling pathways selected by saliva metabolomics, oral disease prediction models can be built through these differential metabolites to carry out early screening, prognosis judgment, and the study of the pathogenesis of oral diseases. Saliva metabolomics is expected to provide a non-invasive method for the diagnosis of oral diseases, which has important clinical significance.

Key words: salivary metabolomics, oral disease, biomarkers

CLC Number: 

  • R 78

TrendMD: 

Tab 1

Research methods, differential metabolites and metabolic pathways in oral disease diagnosis based on salivary metabolomics"

研究

疾病

作者研究对象研究方法差异代谢物相关代谢途径
表达上调表达下调
OSCCWang等[11]OSCC组及健康对照组各30例UPLC-MS乳酸、羟基苯乳酸、N-壬酰基甘氨酸、5-羟甲基尿嘧啶、丁二酸、鸟氨酸、己酰肉碱、丙酰胆碱、肉碱4-羟基-L-谷氨酸、N-乙酰-L-苯丙氨酸、鞘氨醇、植物鞘氨醇、S-羧甲基-L-半胱氨酸糖酵解、酪氨酸代谢、脂肪酸氧化、三羧酸循环、尿素循环、β长链脂肪酸的氧化、精氨酸和脯氨酸代谢、苯丙胺酸代谢、鞘脂代谢等
薛佳艺等[14]OSCC组25例，健康对照组20例GC-TOF-MS酪氨酸、乳酸尿酸、核糖、2-羟基丁二酸三羧酸循环等
Song等[10]OSCC组125例，健康对照组124例CPSI-MS乙酰腐胺、 乙酰胺、哌啶、尸胺、腐胺、N1-乙酰精胺、亚精胺、瓜氨酸、5-氨基戊酸、尿刊酸氧化精氨酸、脯氨酸、N-乙酰精胺、二乙酰亚精胺、2-哌啶酸、赖氨酸、精胺、精氨酸、鸟氨酸、组氨酸氨酰基-tRNA的生物合成、精氨酸/脯氨酸代谢、精氨酸生物合成、赖氨酸降解、组氨酸代谢
OSCC和OLPIshikawa等[16]OSCC组34例，OLP组26例CE-MSN-氧化三甲胺、丁二胺、肌酐、5‐氨基戊酸酯、甲基哌啶、N-乙酰基腐胺、γ-丁酰甜菜碱、吲哚-3-乙酸、N1‐乙酰精胺、2’‐脱氧肌苷、磷酸乙醇胺、N-乙酰基葡糖胺N-乙酰-L-组氨酸、乙酰左旋肉碱鞘脂代谢、精氨酸/脯氨酸代谢、谷胱甘肽代谢、赖氨酸分解、甘油磷脂代谢、嘌呤代谢
OLP王晓霜[18]OLP 120例，健康受试者125例UHPLC-Q-Orbitrap HRMS谷氨酸、焦谷氨酸、柠檬酸、牛磺酸、鸟氨酸、尿酸、乙酰左旋肉碱、次黄嘌呤、磷酸、肌酸、磷酰乙醇胺等植物鞘氨醇d-谷氨酰胺代谢，d-谷氨酸代谢，牛磺酸和次牛磺酸代谢，精氨酸和脯氨酸代谢，丙氨酸、天门冬氨酸和谷氨酸代谢，精氨酸生物合成，甘油磷脂代谢
OLKWei等[19]OLK 32例，健康受试者34例Q/TOF-MS异亮氨酸、N-四癸酸、苯氨基丙酸、苏氨酸、同型半胱氨酸、4-甲氧基苯乙酸酸
Sridharan等[20]OLK 21例，健康受试者18例Q/TOF—LC/MS甲基组氨酸、三磷酸肌醇、甘油酸二磷酸、氧化4-硝基喹啉-1-氧化物、氧化精氨酸、去甲可卡因硝基氧、1-磷酸鞘氨醇、假尿嘧啶L-同型半胱氨酸、泛醌、神经氨酸、戊酸雌二醇碳水化合物代谢、核苷酸代谢、神经鞘脂代谢、雌激素代谢和蛋白质信号代谢
RAULi等[21]RAU 45例，健康受试者49例LC-MS/MS色胺、5-甲氧基色胺硫酸雌酮、硫酸脱氢表雄酮色氨酸代谢、类固醇激素生物合成和其他代谢途径
舍格伦综合征Herrala等[24]舍格伦综合征14例，健康受试者15例NMRS胆碱、牛磺酸、甘氨酸、丙氨酸
早期儿童龋病Schulz等[31]龋病儿童21例，龋病已充填儿童18例，健康儿童18例UPLC-MS/MS焦糖、半乳糖、葡萄糖、甘露糖、棕榈酸、亚油酸、油酸、硬脂酸盐
慢性根尖周炎Montis等[35]慢性根尖周炎并发窦道者11例，健康对照者8例GC/MC4-羟基肉桂酸、N-乙酰神经氨酸、类肌醇、鸟氨酸、腐胺、次黄嘌呤、5-氨基戊酸、脯氨酸、尿嘧啶、赖氨酸、硬脂酸、苏氨酸、尿酸、甘氨酸和磷酸乙醇胺山梨醇、麦芽糖、葡萄糖、木糖醇、琥珀酸、乙醇胺、乳酸、棕榈酸、柠檬酸、尿素、丙二醇和丁二醇嘌呤核苷酸循环、氨基糖和核苷酸代谢、戊糖磷酸途径、糖酵解和糖异生途径
OIEARRZhou等[36]OIEARR患者8例，健康对照者11例NMRS丁酸、丙烷-1,2-二醇、α-亚麻酸、α-葡萄糖、尿酸、富马酸、甲酸盐、鸟苷、嘌呤等

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1 Hyvärinen E, Savolainen M, Mikkonen JJW, et al. Salivary metabolomics for diagnosis and monitoring diseases: challenges and possibilities[J]. Metaboli-tes, 2021, 11(9): 587.
2 Zhang XN, Li BB. Updates of liquid biopsy in oral cancer and multiomics analysis[J]. Oral Dis, 2023, 29(1): 51-61.
3 Chen X, Yu DS. Metabolomics study of oral cancers[J]. Metabolomics, 2019, 15(2): 22.
4 姜啸龙. 质谱仪的发展研究报告[D]. 北京: 北京工业大学, 2017.
Jiang XL. Development research report of mass spectrometer[D]. Beijing: Beijing University of Te-chnology, 2017.
5 朱明华, 胡坪. 仪器分析[M]. 4版. 北京: 高等教育出版社, 2008: 201-211.
Zhu MH, Hu P. Instrumental analysis[M]. 4th ed. Beijing: Higher Education Press, 2008: 201-211.
6 许国旺.代谢组学: 方法与应用[M]. 5版. 北京: 科学出版社, 2020: 105-118.
Xu GW. Metabolomics methods and applications[M]. 5th ed. Beijing: Science Press, 2020: 105-118.
7 刘约权. 现代仪器分析[M]. 3版. 北京: 高等教育出版社, 2015: 357-368.
Liu YQ. Contemporary instrumental analysis[M]. 3rd ed. Beijing: Higher Education Press, 2015: 357-368.
8 于世凤. 口腔组织病理学[M]. 7版. 北京: 人民卫生出版社, 2012: 265-267.
Yu SF. Oral histopathology[M]. 7th ed. Beijing: People’s Medical Publishing House, 2012: 265-267.
9 Mikkonen JJ, Singh SP, Herrala M, et al. Salivary metabolomics in the diagnosis of oral cancer and periodontal diseases[J]. J Periodontal Res, 2016, 51(4): 431-437.
10 Song X, Yang X, Narayanan R, et al. Oral squamous cell carcinoma diagnosed from saliva metabolic profiling[J]. Proc Natl Acad Sci U S A, 2020, 117(28): 16167-16173.
11 Wang QH, Gao P, Wang XY, et al. The early diagnosis and monitoring of squamous cell carcinoma via saliva metabolomics[J]. Sci Rep, 2014, 4: 6802.
12 Lin L, Huang ZZ, Gao Y, et al. LC-MS based serum metabonomic analysis for renal cell carcinoma diagnosis, staging, and biomarker discovery[J]. J Proteome Res, 2011, 10(3): 1396-1405.
13 Ryland LK, Fox TE, Liu X, et al. Dysregulation of sphingolipid metabolism in cancer[J]. Cancer Biol Ther, 2011, 11(2): 138-149.
14 薛佳艺, 朱晓燕, 危常磊, 等. 25例口腔鳞癌患者唾液代谢组学分析[J]. 上海口腔医学, 2021, 30(2): 201-205.
Xue JY, Zhu XY, Wei CL, et al. Study of salivary metabonomics in patients with oral squamous cell carcinoma and leukoplakia[J]. Shanghai J Stomatol, 2021, 30(2): 201-205.
15 Yan SK, Wei BJ, Lin ZY, et al. A metabonomic approach to the diagnosis of oral squamous cell carcinoma, oral lichen planus and oral leukoplakia[J]. Oral Oncol, 2008, 44(5): 477-483.
16 Ishikawa S, Sugimoto M, Edamatsu K, et al. Discrimination of oral squamous cell carcinoma from oral lichen planus by salivary metabolomics[J]. Oral Dis, 2020, 26(1): 35-42.
17 Nema R, Vishwakarma S, Agarwal R, et al. Emer-ging role of sphingosine-1-phosphate signaling in head and neck squamous cell carcinoma[J]. Onco Targets Ther, 2016(9): 3269-3280.
18 王晓霜. 口腔扁平苔藓患者的血清、唾液代谢组学研究[D]. 郑州: 郑州大学, 2020: 71.
Wang XS. Study on metabolomics of serum and saliva in patients with oral lichen planus[D]. Zhengzhou: Zhengzhou University, 2020: 71.
19 Wei J, Xie GX, Zhou ZT, et al. Salivary metabolite signatures of oral cancer and leukoplakia[J]. Int J Cancer, 2011, 129(9): 2207-2217.
20 Sridharan G, Ramani P, Patankar S, et al. Evaluation of salivary metabolomics in oral leukoplakia and oral squamous cell carcinoma[J]. J Oral Pathol Med, 2019, 48(4): 299-306.
21 Li YT, Wang DM, Zeng CW, et al. Salivary metabolomics profile of patients with recurrent aphthous ulcer as revealed by liquid chromatography-tandem mass spectrometry[J]. J Int Med Res, 2018, 46(3): 1052-1062.
22 Jiang XL, Zhong W, An HY, et al. Attenuated DHEA and DHEA-S response to acute psychosocial stress in individuals with depressive disorders[J]. J Affect Disord, 2017, 215: 118-124.
23 Ozyurt K, Çelik A, Sayarlıoglu M, et al. Serum Th1, Th2 and Th17 cytokine profiles and alpha-enolase levels in recurrent aphthous stomatitis[J]. J Oral Pathol Med, 2014, 43(9): 691-695.
24 Herrala M, Mikkonen JJW, Pesonen P, et al. Variability of salivary metabolite levels in patients with Sjögren’s syndrome[J]. J Oral Sci, 2021, 63(1): 22-26.
25 Fragkioudaki S, Mavragani CP, Moutsopoulos HM. Predicting the risk for lymphoma development in Sjögren syndrome: an easy tool for clinical use[J]. Medicine (Baltimore), 2016, 95(25): e3766.
26 Mozaffari MS, Borke JL. Taurine in submandibular gland of the rat: effect of muscarinic drugs[J]. J Histochem Cytochem, 2002, 50(4): 527-532.
27 Hynne H, Sandås EM, Elgstøen KBP, et al. Saliva metabolomics in dry mouth patients with head and neck cancer or Sjögren’s syndrome[J]. Cells, 2022, 11(3): 323.
28 Fernández-Ochoa Á, Borrás-Linares I, Quirantes-Piné R, et al. Discovering new metabolite alterations in primary Sjögren’s syndrome in urinary and plasma samples using an HPLC-ESI-QTOF-MS methodology[J]. J Pharm Biomed Anal, 2020, 179: 112999.
29 Mondanelli G, Iacono A, Carvalho A, et al. Amino acid metabolism as drug target in autoimmune di-seases[J]. Autoimmun Rev, 2019, 18(4): 334-348.
30 Pereira LF, de Deus Moura Lima M, de Moura MS, et al. Does outpatient dental treatment have impact on the quality of life of children with early childhood caries[J]. Clin Oral Invest, 2022, 26(2): 1605-1612.
31 Schulz A, Lang R, Behr J, et al. Targeted metabolomics of pellicle and saliva in children with different caries activity[J]. Sci Rep, 2020, 10: 697.
32 Aimetti M, Cacciatore S, Graziano A, et al. Metabonomic analysis of saliva reveals generalized chronic periodontitis signature[J]. Metabolomics, 2012, 8(3): 465-474.
33 Andörfer L, Holtfreter B, Weiss S, et al. Salivary metabolites associated with a 5-year tooth loss identified in a population-based setting[J]. BMC Med, 2021, 19(1): 161.
34 Sakanaka A, Kuboniwa M, Hashino E, et al. Distinct signatures of dental plaque metabolic by pro-ducts dictated by periodontal inflammatory status[J]. Sci Rep, 2017(7): 42818.
35 Montis N, Cotti E, Noto A, et al. Salivary metabolomics fingerprint of chronic apical abscess with sinus tract: a pilot study[J]. Sci World J, 2019, 2019: 3162063.
36 Zhou JL, Hu HM, Huang RH. A pilot study of the metabolomic profiles of saliva from female ortho-dontic patients with external apical root resorption[J]. Clin Chimica Acta, 2018(478): 188-193.
37 Quartieri E, Casali E, Ferrari E, et al. Sample optimization for saliva 1H-NMR metabolic profiling[J]. Anal Biochem, 2022, 640: 114412.
38 Di Minno A, Gelzo M, Caterino M, et al. Challen-ges in metabolomics-based tests, biomarkers revealed by metabolomic analysis, and the promise of the application of metabolomics in precision medicine[J]. Int J Mol Sci, 2022, 23(9): 5213.
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