Chinese Medical Sciences Journal ›› 2024, Vol. 39 ›› Issue (1): 19-28.doi: 10.24920/004338
田艺超1,郭春岚1,李珍1,尤欣2,刘晓燕3,苏金梅2,赵斯佳1,穆月1,孙伟3,*(),李倩1,*()
收稿日期:
2024-01-15
接受日期:
2024-03-08
出版日期:
2024-03-31
通讯作者:
孙伟,李倩
Yi-Chao Tian1,Chun-Lan Guo1,Zhen Li1,Xin You2,Xiao-Yan Liu3,Jin-Mei Su2,Si-Jia Zhao1,Yue Mu1,Wei Sun3,*(),Qian Li1,*()
Received:
2024-01-15
Accepted:
2024-03-08
Published:
2024-03-31
Contact:
* Qian Li E-mail: 摘要:
目的 唾液腺是原发性干燥综合征(pSS)的主要靶器官,因此唾液被认为是腺体病理生理学和疾病状态的镜子。本研究旨在说明pSS患者的唾液蛋白质组学特征,并鉴定可能辅助诊断的潜在生物标志物。
方法 发现集包含49个样本[24个来自pSS,25个来自年龄和性别匹配的健康对照(HCs)],验证集包括25个样本(12个来自pSS,13个来自HCs)。36 例 pSS 患者和 38 例健康对照者以 2:1 的比例集中随机分配至 Discovery 组或验证组。在2D LC-HRMS/MS平台上使用数据非依赖性采集(DIA)策略分析来自pSS患者和健康对照组的未刺激性全唾液样本,以揭示差异蛋白。根据基因本体(GO)分析和国际药学文摘(IPA)分析的蛋白质注释,使用DIA分析验证了关键蛋白质。随机森林用于建立SS的预测模型。
结果 共发现1,963个蛋白,其中136个蛋白在pSS患者中表现出差异性。生物信息学研究表明这些蛋白质主要与免疫功能、新陈代谢和炎症有关。一组19个蛋白质生物标志物通过基于P 值和随机森林的排序顺序进行鉴定,并验证为具有特殊曲线下面积 (AUC) 值(发现集:0.817;验证集:0.882)的潜在生物标志物,可用于鉴别pSS 患者和健康对照人群。
结论 新发现的候选蛋白组合可能有助于pSS的诊断。唾液蛋白质组学分析是一种很有前途的无创方法,可用于对pSS患者进行预后评估以及早期和精确治疗。DIA具备最佳的时间效率和数据可靠性,可望成为未来唾液蛋白质组研究的合适选择。
Yi-Chao Tian, Chun-Lan Guo, Zhen Li, Xin You, Xiao-Yan Liu, Jin-Mei Su, Si-Jia Zhao, Yue Mu, Wei Sun, Qian Li. Data-Independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Salivary Biomarkers of Primary Sjögren’s Syndrome[J].Chinese Medical Sciences Journal, 2024, 39(1): 19-28.
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Characteristics | pSS group | HCs group | t/X2 | P value | |||
---|---|---|---|---|---|---|---|
Discovery (n=24) | Validation (n=12) | Discovery (n=25) | Validation (n=13) | ||||
Age, yrs, mean±SD | 41.1±10.9 | 40.6±12.8 | 41.4±12.2 | 44.1±12.7 | 0.049 | 0.88 | |
Sex, females [n(%)] | 21(87.5) | 10(83.3) | 23 (92) | 12 (92.3) | 0.075 | 0.60 | |
Anti-SSA/Ro antibody + [n(%)] | 16(66.7) | 9(75.0) | / | / | 0.574 | 0.682 | |
Anti-SSB/La antibody + [n(%)] | 3(12.5) | 1(8.3) | / | / | 0.112 | 1 | |
Immunoglobulin G + [n(%)] | 12(50.0) | 6(50.0) | / | / | 0 | 1 | |
Labial gland biopsy + [n(%)] | 13(54.2) | 9(75.0) | / | / | 2.595 | 0.205 |
"
No. | Protein name | AUC | P value | Fold change |
---|---|---|---|---|
1 | Q13217 | 0.86285 | 0.002438 | 2.0129 |
2 | P01034 | 0.85764 | 0.006314 | 2.6949 |
3 | P07711 | 0.85243 | 0.001923 | 1.831 |
4 | P09958 | 0.85069 | 0.001031 | 1.8654 |
5 | P28065 | 0.85069 | 7.72E-06 | -1.2467 |
6 | O43852 | 0.84201 | 6.80E-04 | 1.4389 |
7 | O43505 | 0.83854 | 2.39E-04 | 1.4676 |
8 | P25789 | 0.82812 | 9.41E-05 | -1.276 |
9 | Q9UBX7 | 0.81771 | 0.00464 | 1.3578 |
10 | Q9NRJ3 | 0.81597 | 0.024021 | 1.4358 |
11 | P35030 | 0.81424 | 0.001265 | 1.3919 |
12 | P12109 | 0.8125 | 0.008958 | 1.3342 |
13 | O75976 | 0.80903 | 6.50E-04 | 1.3292 |
14 | Q92743 | 0.80035 | 0.46752 | 1.0645 |
15 | P16870 | 0.7934 | 0.001147 | 1.3544 |
16 | P13798 | 0.78646 | 5.01E-04 | -1.0262 |
17 | P01011 | 0.75347 | 0.018898 | 2.5295 |
18 | P32320 | 0.74306 | 0.001919 | -0.88055 |
19 | P08670 | 0.73785 | 0.006534 | -1.581 |
1. | González S, Sung H, Sepúlveda D, et al. Oral manifestations and their treatment in Sjögren’s syndrome. Oral Dis 2014; 20: 153-61. doi: 10.1111/odi.12105. |
2. | Brito-Zerón P, Baldini C, Bootsma H, et al. Sjögren syndrome. Nat Rev Dis Primers 2016; 2: 16047. doi: 10.1016/j.medcli.2022.10.007. |
3. | Soret P le Dantec C, Desvaux E, et al. A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome. Nat Commun 2021; 12: 3523. doi: 10.1038/s41467-021-23472-7. |
4. |
Vitorino R, Lobo MJC, Ferrer-Correira AJ, et al. Identification of human whole saliva protein components using proteomics. Proteomics 2004; 4: 1109-15. doi:10.1002/pmic.200300638.
pmid: 15048992 |
5. |
Malamud D. Saliva as a diagnostic fluid. BMJ 1992; 305: 207-8. doi:10.1016/j.cden.2010.08.004.
pmid: 1290500 |
6. |
Loo J A, Yan W, Ramachandran P, et al. Comparative human salivary and plasma proteomes. J Dent Res 2010; 89: 1016-23. doi:10.1177/0022034510380414.
pmid: 20739693 |
7. | Hu S, Vissink A, Arellano M, et al. Identification of autoantibody biomarkers for primary Sjögren’s syndrome using protein microarrays. Proteomics 2011; 11: 1499-507. doi:10.1002/pmic.201000206. |
8. |
Deutsch O, Krief G, Konttinen YT, et al. Identification of Sjögren’s syndrome oral fluid biomarker candidates following high-abundance protein depletion. Rheumatology (Oxford) 2015; 54: 884-90. doi: 10.1093/rheumatology/keu405.
pmid: 25339641 |
9. | Katsiougiannis S, Wong DTW. The proteomics of saliva in Sjögren’s syndrome. Rheum Dis Clin North Am 2016; 42: 449-56. doi:10.1016/j.rdc.2016.03.004. |
10. | Jonsson R, Brokstad KA, Jonsson MV, et al. Current concepts on Sjögren’s syndrome - classification criteria and biomarkers. Eur J Oral Sci 2018; 126 Suppl 1: 37-48. doi: 10.1111/eos.12536. |
11. |
Ferraccioli G, de Santis M, Peluso G, et al. Proteomic approaches to Sjögren’s syndrome: a clue to interpret the pathophysiology and organ involvement of the disease. Autoimmun Rev 2010; 9: 622-6. doi:10.1016/j.autrev.2010.05.010.
pmid: 20462525 |
12. |
Baldini C, Giusti L, Bazzichi L, et al. Proteomic analysis of the saliva: a clue for understanding primary from secondary Sjögren’s syndrome? Autoimmun Rev 2008; 7: 185-91. doi: 10.1016/j.autrev.2007.11.002.
pmid: 18190876 |
13. | Chen WQn, Cao H, Lin J, et al. Biomarkers for primary Sjögren’s syndrome. Genomics Proteomics Bioinformatics 2015; 13: 219-23. doi: 10.2217/bmm-2017-0297. |
14. |
Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet 2012; 13: 227-32. doi: 10.1038/nrg3185.
pmid: 22411467 |
15. |
Callister SJ, Barry RC, Adkins JN, et al. Normalization approaches for removing systematic biases associated with mass spectrometry and label-free proteomics. J Proteome Res 2006; 5: 277-86. doi: 10.1021/pr050300l.
pmid: 16457593 |
16. | Maddali BS, Campana G, D’Agata A, et al. The diagnosis value of beta 2-microglobulin and immunoglobulins in primary Sjögren’s syndrome. Clin Rheumatol 1995; 14: 151-6. doi: 10.1007/BF02214934. |
17. |
Baldini C, Gallo A, Perez P, et al. Saliva as an ideal milieu for emerging diagnostic approaches in primary Sjögren’s syndrome. Clin Exp Rheumatol 2012; 30: 785-90.
pmid: 23009763 |
18. | Jin YB, Dai YJ, Chen JL, et al. Anti-carbonic anhydrase II antibody reflects urinary acidification defect especially in proximal renal tubules in patients with primary Sjögren syndrome. Medicine (Baltimore) 2023; 102: e32673. doi: 10.1097/MD.0000000000032673. |
19. | Qin BD, Wang JQ, Yang ZX, et al. Epidemiology of primary Sjögren’s syndrome: a systematic review and meta-analysis. Ann Rheum Dis 2015; 74: 1983-9. doi: 10.1136/annrheumdis-2014-205375. |
20. | Goules AV, Tzioufas AG. Primary Sjögren’s syndrome: clinical phenotypes, outcome and the development of biomarkers. Immunol Res 2017; 65: 331-344. doi: 10.1007/s12026-016-8844-4. |
21. | Chaudhury NMA, Proctor GB, Karlsson NG, et al. Reduced mucin-7 (Muc7) sialylation and altered saliva rheology in sjögren’s syndrome associated oral dryness. Mol Cell Proteomics 2016; 15: 1048-59. doi:10.1074/mcp.M115.052993. |
22. | Horvatovich P, Végvári Á, Saul J, et al. In vitro transcription/translation system: a versatile tool in the search for missing proteins. J Proteome Res 2015; 14: 3441-51. doi:10.1021/acs.jproteome.5b00486. |
23. | Meyer JG, D’Souza AK, Sorensen DJ, et al. Quantification of lysine acetylation and succinylation stoichiometry in proteins using mass spectrometric data-independent acquisitions (SWATH). J Am Soc Mass Spectrom 2016; 27: 1758-1771. doi:10.1007/s13361-016-1476-z. |
24. | Gao TG, Lou CX, Wang Y, et al. Anti-carbonic anhydrase goldbodies by conformational reconstruction of the complementary-determining regions of phage-displayed antibodies. ChemMedChem 2023; 18: e202300185. doi:10.1002/cmdc.202300185. |
25. | Guo ZG, Liu XJ, Li ML, et al. Differential urinary glycoproteome analysis of type 2 diabetic nephropathy using 2D-LC-MS/MS and iTRAQ quantification. J Transl Med 2015; 13: 371. doi: 10.1186/s12967-015-0712-9. |
26. | Xiao XP, Liu YR, Guo ZG, et al. Comparative proteomic analysis of the influence of gender and acid stimulation on normal human saliva using LC/MS/MS. Proteomics Clin Appl 2017; 11: undefined. doi: 10.1002/prca.201600142. |
Garza-García F, Delgado-García G, Garza-Elizondo M, et al. Salivary β2-microglobulin positively correlates with ESSPRI in patients with primary Sjögren’s syndrome. Rev Bras Reumatol Engl Ed 2017; 57: 182-4. doi: 10.1016/j.rbre.2016.11.001. | |
27. | Thatayatikom A, Jun I, Bhattacharyya I, et al. The diagnostic performance of early Sjögren’s syndrome autoantibodies in juvenile Sjögren’s syndrome: The University of Florida Pediatric Cohort study. Front Immunol 2021; 12: 704193. doi:10.3389/fimmu.2021.704193. |
28. | Margaretten M. Neurologic manifestations of primary Sjögren syndrome. Rheum Dis Clin North Am 2017; 43: 519-29. doi: 10.1016/j.rdc.2017.06.002. |
29. | Silva LM, Clements JA. Mass spectrometry based proteomics analyses in kallikrein-related peptidase research: implications for cancer research and therapy. Expert Rev Proteomics 2017; 14: 1119-30. doi:10.1080/14789450.2017.1389637. |
30. | Botrè F, Botrè C, Podestà E, et al. Effect of anti-carbonic anhydrase antibodies on carbonic anhydrases I and II. Clin Chem 2003; 49: 1221-3. doi: 10.1373/49.7.1221. |
31. |
Makino K, Jinnin M, Makino T, et al. Serum levels of soluble carbonic anhydrase IX are decreased in patients with diffuse cutaneous systemic sclerosis compared to those with limited cutaneous systemic sclerosis. Biosci Trends 2014; 8: 144-8. doi: 10.5582/bst.2014.01020.
pmid: 25030848 |
32. |
Aparisi L, Farre A, Gomez-Cambronero L, et al. Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis. Gut 2005; 54: 703-9. doi: 10.1136/gut.2004.047142.
pmid: 15831920 |
33. |
Invernizzi P, Selmi C, Zuin M, et al. Lack of serum antibodies to membrane bound carbonic anhydrase IV in patients with primary biliary cirrhosis. Gut 2005; 54: 1665. doi: 10.1136/gut.2005.072389.
pmid: 16227372 |
34. | Gillet LC, Navarro P, Tate S, et al. Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol Cell Proteomics 2012; 11: O111.016717. doi: 10.1074/mcp.O111.016717. |
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