## 6 Salivary Proteomics: Techniques and Applications
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**References** & **Study Design** & **Sample Size** & **Method of Analysis** & **Variation in the Proteomic Profile** \\ \hline Bostanci & Cross-sectional & 17 CP, 17 AgP; & Mass & Lactoferrin, lacitrin, sCD14, Mucin & \\ et al. [107] & study & 16 controls & spectrometry-based & 5B, and Mucin 7 down-regulated in & \\  & & 16 controls & untargeted proteomics & AP and SL4A1 was upregulated. & \\  & & & & & \\ Mertens & Cross-sectional & 10 CP, 11 AgP; & Mass & Chromesium SN higher in controls & \\ et al. [109] & study & 12 controls. & 13 spectrometry-based & \(\alpha\)-fibrinogen were higher in & \\  & & 12 controls. & untargeted proteomics. & periodontitis patients. \\  & & & & \\ Tang et al. [110] & Cross-sectional & 16 cases, 17 controls. & Mass & \\  & & 16 cases, 17 controls. & spectrometry-based & \\  & & & & \\  & & & & \\ Antezack & Cross-sectional & & Mass & \\ et al. [111] & study & 67 cases, 74 controls & spectrometry-based & No identification of specific proteins \\  & & & & \\ Hartenbach & Cross-sectional & & Mass & \\ et al. [112] & study & 30 cases, 10 controls. & spectrometry-based & \\  & & & & \\  & & & & \\ Grant & Cross-sectional & 10 MMP, 10 AP; & Mass & MMP9, S100A8, A1 AGP, and \\ et al. [103] & study & 10 controls. & spectrometry-based & pyruvate kinase higher in \\  & & 10 controls. & untargeted proteomics. & periodontitis patients. \\ Casarin & Cross-sectional & & Mass & GHG1, CSTB, KKT9, SMR3B, \\ et al. [113] & study & 12 cases, 13 controls & spectrometry-based & IGHG4, and SERPINA1 were higher & \\  & & & untargeted proteomics & in periodontitis patients. \\ Romano & Cross-sectional & 15 UP, 15 TP; & Mass & Cystatin SN higher in healthy \\ et al. [106] & study & 15 controls. & spectrometry-based & patients and in patients under \\  & & & untargeted proteomics. & periodontal active treatment. \\ Goncalves & Cross-sectional & & Mass & Periodontitis patients had higher \\ et al. [114] & study & 10 cases, 10 controls & Mass & levels of albumin, hemoglobin, and \\  & & & & \\ et al. [115] & study & 10 cases, 10 controls & spectrometry-based & immunoglobulin, and they had a \\  & & & untargeted proteomics & lower abundance of cystatin \\  & & & compared to the control group. \\  & & & & \\  & & & \\ Salazar & Cross-sectional & & Mass & \\ et al. [96] & study & 20 cases, 20 controls. & spectrometry-based & alpha-2-HS-glycoprotein, fibrinogen \\  & & & untargeted proteomics & alpha chain higher in periodontitis \\  & & & & \\ Chaiyarit & Cross-sectional & & Mass & \\ et al. [115] & study & 30 cases, 30 controls. & spectrometry-based & No identification of specific proteins \\  & & & \\  & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 5: _Cont._had a bias-corrected accuracy (bc-ACC) of 78.8-86.8% (bc-sensitivity/bc-specificity of 62.5-86.9%/60.9-98.1%) to diagnose periodontitis. Predictive capacity increased more by adjusting for age (bc-ACC: 94.1-98.2%; bc-sensitivity/bc-specificity: 90.2-98.6%/93.6-97.2%) than smoking (bc-ACC: 83.9-90.4%; bc-sensitivity/bc-specificity: 73.6-89.9%/76.2-96.4%). The proteins involved were as follows: keratin, type II cytoskeletal 1, protein S100-A8, \(\beta\)-2-microglobulin, neutrophil defensin 1, lysozyme C, ubiquitin-60S ribosomal protein L40, isoform 2 of tropomyosin \(\alpha\)-3 chain, and resistin. Two dual combinations showed bc-sensitivity/bc-specificity of \(>\)90%: \(\beta\)-2-microglobulin with profilin-1, and lysozyme C with zymogen granule protein 16 homologue B. Thus, the authors concluded that salivary biomarkers have good diagnostic relevance, and that age is better than smoking in influencing the accuracy of the single biomarkers. Moreover, they also added that clinical diagnosis remains the gold standard, but untargeted analysis may be helpful in early diagnosis, considering the lack of clinical signs at early stages and the elevated accuracy of the untargeted method.