477
Views
0
CrossRef citations to date
0
Altmetric
Review

Shaping the future of oral cancer diagnosis: advances in salivary proteomics

, , , &
Pages 149-168 | Received 24 Sep 2023, Accepted 19 Feb 2024, Published online: 24 Apr 2024

References

  • Julian RS, Woo BM, Rabey EC. Oral Cavity and Oropharyngeal Cancer: Etiology, Diagnosis and Staging. J California Dental Association. 2021;49(3):163–170. doi: 10.1080/19424396.2021.12222685
  • Rivera C. Essentials of oral cancer. Int J Clin Exp Pathol. 2015;8(9):11884–11894.
  • Michalke B, Rossbach B, Göen T, et al. Saliva as a matrix for human biomonitoring in occupational and environmental medicine. Int Arch Occup Environ Health. 2015;88(1):1–44. doi: 10.1007/s00420-014-0938-5
  • Rao PV, Reddy AP, Lu X, et al. Proteomic identification of salivary biomarkers of type-2 diabetes. J Proteome Res. 2009;8(1):239–245. doi: 10.1021/pr8003776
  • Pfaffe T, Cooper-White J, Beyerlein P, et al. Diagnostic potential of saliva: current state and future applications. Clin Chem. 2011;57(5):675–687. doi: 10.1373/clinchem.2010.153767
  • Scarano E, Fiorita A, Picciotti PM, et al. Proteomics of saliva: personal experience. Acta Otorhinolaryngol Ital. 2010;30(3):125–130.
  • Castagnola M, Picciotti PM, Messana I, et al. Potential applications of human saliva as diagnostic fluid. Acta Otorhinolaryngol Ital. 2011;31(6):347–357.
  • Laine M, Pienihakkinen K, Leimola-Virtanen R. The effect of repeated sampling on paraffin-stimulated salivary flow rates in menopausal women. Arch Oral Biol. 1999;44(1):93–95. doi: 10.1016/S0003-9969(98)00097-1
  • Topkas E, Keith P, Dimeski G, et al. Evaluation of saliva collection devices for the analysis of proteins. Clin Chim Acta. 2012;413(13–14):1066–1070. doi: 10.1016/j.cca.2012.02.020
  • Amado F, Lobo MJ, Domingues P, et al. Salivary peptidomics. Expert Rev Proteomics. 2010;7(5):709–721. doi: 10.1586/epr.10.48
  • Granger DA, Kivlighan KT, Fortunato C, et al. Integration of salivary biomarkers into developmental and behaviorally-oriented research: problems and solutions for collecting specimens. Physiol Behav. 2007;92(4):583–590. doi: 10.1016/j.physbeh.2007.05.004
  • Ferguson DB. Current diagnostic uses of saliva. J Dent Res. 1987;66(2):420–424. doi: 10.1177/00220345870660020601
  • Khurshid Z, Zohaib S, Najeeb S, et al. Human saliva collection devices for proteomics: an update. Int J Mol Sci. 2016;17(6):846. doi: 10.3390/ijms17060846
  • Bellagambi FG, Lomonaco T, Salvo P, et al. Saliva sampling: methods and devices. An overview. Trends Analyt Chem. 2020;124:115781. doi: 10.1016/j.trac.2019.115781
  • Baum BJ. Evaluation of stimulated parotid saliva flow rate in different age groups. J Dent Res. 1981;60(7):1292–1296. doi: 10.1177/00220345810600070101
  • Khurshid Z, Moin SF, Khan RS, et al. Human salivary protein extraction from RNAPro.SAL, Pure.SAL, and passive drooling method. Eur J Dent. 2017;11(3):385–389. doi: 10.4103/ejd.ejd_183_17
  • Heinzerling CI, Stieger M, Bult JH, et al. Individually modified saliva delivery changes the perceived intensity of saltiness and sourness. Chem Percept. 2011;4(4):145–153. doi: 10.1007/s12078-011-9099-z
  • Henson BS, Wong DT. Collection, storage, and processing of saliva samples for downstream molecular applications. Methods Mol Biol. 2010;666:21–30.
  • Chevalier F, Hirtz C, Chay S, et al. Proteomic studies of saliva: a proposal for a standardized handling of clinical samples. Clin Proteomics. 2007;3(1–4):13–21. doi: 10.1007/s12014-007-9000-x
  • Schipper RG, Silletti E, Vingerhoeds MH. Saliva as research material: biochemical, physicochemical and practical aspects. Arch Oral Biol. 2007;52(12):1114–1135. doi: 10.1016/j.archoralbio.2007.06.009
  • Chiang SH, Thomas GA, Liao W, et al. Rnapro*sal: a device for rapid and standardized collection of saliva RNA and proteins. Biotechniques. 2015;58(2):69–76. doi: 10.2144/000114254
  • Xiao H, Wong DT. Method development for proteome stabilization in human saliva. Anal Chim Acta. 2012;722:63–69. doi: 10.1016/j.aca.2012.02.017
  • Esser D, Alvarez-Llamas G, de Vries MP, et al. Sample stability and protein composition of saliva: implications for its use as a diagnostic fluid. Biomark Insights. 2008;3:25–27. doi: 10.4137/BMI.S607
  • Janardhanam SB, Zunt SL, Srinivasan M. Quality assessment of saliva bank samples. Biopreserv Biobank. 2012;10(3):282–287. doi: 10.1089/bio.2011.0039
  • Kawashima Y, Fukutomi T, Tomonaga T, et al. High-yield peptide-extraction method for the discovery of subnanomolar biomarkers from small serum samples. J Proteome Res. 2010;9(4):1694–1705. doi: 10.1021/pr9008018
  • Carrillo-Rodriguez P, Selheim F, Hernandez-Valladares M. Mass spectrometry-based proteomics workflows in cancer research: the relevance of choosing the right steps. Cancers (Basel). 2023;15(2):555. doi: 10.3390/cancers15020555
  • Brunelle JL, Green R. One-dimensional SDS-polyacrylamide gel electrophoresis (1D SDS-PAGE). Methods Enzymol. 2014;541:151–159.
  • Magdeldin S, Enany S, Yoshida Y, et al. Basics and recent advances of two dimensional- polyacrylamide gel electrophoresis. Clin Proteomics. 2014;11(1):16. doi: 10.1186/1559-0275-11-16
  • Arentz G, Weiland F, Oehler MK, et al. State of the art of 2D DIGE. Proteomics Clin Appl. 2015;9(3–4):277–288. doi: 10.1002/prca.201400119
  • Shi Y, Xiang R, Horvath C, et al. The role of liquid chromatography in proteomics. J Chromatogr A. 2004;1053(1–2):27–36. doi: 10.1016/S0021-9673(04)01204-X
  • Banerjee S, Mazumdar S. Electrospray ionization mass spectrometry: a technique to access the information beyond the molecular weight of the analyte. Int J Anal Chem. 2012;2012:282574. doi: 10.1155/2012/282574
  • Li D, Yi J, Han G, et al. MALDI-TOF mass spectrometry in clinical analysis and research. ACS Meas Sci Au. 2022;2(5):385–404. doi: 10.1021/acsmeasuresciau.2c00019
  • Neagu AN, Jayathirtha M, Baxter E, et al. Applications of Tandem Mass Spectrometry (MS/MS) in protein analysis for biomedical research. Molecules. 2022;27(8):2411. doi: 10.3390/molecules27082411
  • Carnielli CM, Macedo CCS, De Rossi T, et al. Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer. Nat Commun. 2018;9(1):3598. doi: 10.1038/s41467-018-05696-2
  • Birhanu AG. Mass spectrometry-based proteomics as an emerging tool in clinical laboratories. Clin Proteomics. 2023;20(1):32. doi: 10.1186/s12014-023-09424-x
  • Lou R, Shui W. Acquisition and analysis of DIA-Based proteomic data: a comprehensive survey in 2023. Mol Cell Proteomics. 2024;23(2):100712. doi: 10.1016/j.mcpro.2024.100712
  • Murray KK, Boyd RK, Eberlin MN, et al. Definitions of terms relating to mass spectrometry (IUPAC recommendations 2013). Pure Appl Chem. 2013;85(7):1515–1609. doi: 10.1351/PAC-REC-06-04-06
  • Kooren JA, Rhodus NL, Tang C, et al. Evaluating the potential of a novel oral lesion exudate collection method coupled with mass spectrometry-based proteomics for oral cancer biomarker discovery. Clin Proteomics. 2011;8(1):13. doi: 10.1186/1559-0275-8-13
  • Alhendi AS. A review: protein identification by LC-MS: principles, instrumentation, and applications. Iraqi J Sci. 2020;61(10):2448–2466. doi: 10.24996/ijs.2020.61.10.2
  • Chang CY, Picotti P, Huttenhain R, et al. Protein significance analysis in selected reaction monitoring (SRM) measurements. Mol Cell Proteomics. 2012;11(4):M111 014662. doi: 10.1074/mcp.M111.014662
  • Duncan MW, Yergey AL, Patterson SD. Quantifying proteins by mass spectrometry: the selectivity of SRM is only part of the problem. Proteomics. 2009;9(5):1124–1127. doi: 10.1002/pmic.200800739
  • Unwin RD, Griffiths JR, Whetton AD. Simultaneous analysis of relative protein expression levels across multiple samples using iTRAQ isobaric tags with 2D nano LC–MS/MS. Nat Protoc. 2010;5(9):1574–1582. doi: 10.1038/nprot.2010.123
  • Pan S, Aebersold R. Quantitative proteomics by stable isotope labeling and mass spectrometry. Methods Mol Biol. 2007;367:209–218.
  • Chen X, Sun Y, Zhang T, et al. Quantitative proteomics using isobaric labeling: a practical guide. Int J Geno Prot. 2021;19(5):689–706. doi: 10.1016/j.gpb.2021.08.012
  • Chu HW, Chang KP, Hsu CW, et al. Identification of salivary biomarkers for oral cancer detection with untargeted and targeted quantitative proteomics approaches. Mol Cell Proteomics. 2019;18(9):1796–1806. doi: 10.1074/mcp.RA119.001530
  • Shan J, Sun Z, Yang J, et al. Discovery and preclinical validation of proteomic biomarkers in saliva for early detection of oral squamous cell carcinomas. Oral Dis. 2019;25(1):97–107. doi: 10.1111/odi.12971
  • van Leeuwen SJM, Proctor GB, Staes A, et al. The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach. BMC Oral Health. 2023;23(1):460. doi: 10.1186/s12903-023-03190-w
  • St John MA, Li Y, Zhou X, et al. Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngology–Head & Neck Surgery. 2004;130(8):929–935. doi: 10.1001/archotol.130.8.929
  • Kumar P, Gupta S, Das BC. Saliva as a potential non-invasive liquid biopsy for early and easy diagnosis/prognosis of head and neck cancer. Transl Oncol. 2024;40:101827. doi: 10.1016/j.tranon.2023.101827
  • Parker CE, Borchers CH. Mass spectrometry based biomarker discovery, verification, and validation–quality assurance and control of protein biomarker assays. Mol Oncol. 2014;8(4):840–858. doi: 10.1016/j.molonc.2014.03.006
  • Alhajj M, Zubair M, Farhana A. Enzyme Linked Immunosorbent Assay. In: StatPearls. Treasure Island (FL); 2024. https://www.ncbi.nlm.nih.gov/books/NBK555922/
  • Begum H, Murugesan P, Tangutur A. Western blotting: a powerful staple in scientific and biomedical research. Biotechniques. 2022;73(1):58–69. doi: 10.2144/btn-2022-0003
  • Singh KK, Gupta A, Bharti C, et al. Emerging techniques of western blotting for purification and analysis of protein. Future J Pharm Sci. 2021;7(1):239. doi: 10.1186/s43094-021-00386-1
  • Bass JJ, Wilkinson DJ, Rankin D, et al. An overview of technical considerations for Western blotting applications to physiological research. Scandinavian J Med Sci Sports. 2017;27(1):4–25. doi: 10.1111/sms.12702
  • Dunphy K, Dowling P, Bazou D, et al. Current methods of post-translational modification analysis and their applications in blood cancers. Cancers (Basel). 2021;13(8):1930. doi: 10.3390/cancers13081930
  • Ahsan H. Monoplex and multiplex immunoassays: approval, advancements, and alternatives. Comp Clini Pathol. 2022;31(2):333–345. doi: 10.1007/s00580-021-03302-4
  • Huang Y, Zhu H. Protein Array-based Approaches for Biomarker Discovery in Cancer. Int J Geno Prot. 2017;15(2):73–81. doi: 10.1016/j.gpb.2017.03.001
  • Fasolo J, Snyder M. Protein microarrays. Methods Mol Biol. 2009;548:209–222.
  • Honarmand M, Saravani R, Farhad-Mollashahi L, et al. Salivary Lactate Dehydrogenase, C-Reactive Protein, and Cancer Antigen 125 Levels in Patients with oral lichen planus and oral squamous cell carcinoma. International Journal Of Cancer Management. 2021;14(3):e108344. doi: 10.5812/ijcm.108344
  • Chang YT, Chu LJ, Liu YC, et al. Verification of saliva matrix metalloproteinase-1 as a strong diagnostic Marker of oral cavity cancer. Cancers (Basel). 2020;12(8):2273. doi: 10.3390/cancers12082273
  • Faria PCB, Carneiro AP, Binato R, et al. Upregulation of tropomyosin alpha-4 chain in patients’ saliva with oral squamous cell carcinoma as demonstrated by phage display. Sci Rep. 2019;9(1):18399. doi: 10.1038/s41598-019-54686-x
  • Deepthi G, Nandan SR, Kulkarni PG. Salivary tumour necrosis factor-α as a biomarker in oral leukoplakia and oral squamous cell carcinoma. Asian Pac J Cancer Prev. 2019;20(7):2087–2093. doi: 10.31557/APJCP.2019.20.7.2087
  • van der Merwe L, Wan Y, Cheong HJ, et al. A pilot study to profile salivary angiogenic factors to detect head and neck cancers. BMC Cancer. 2018;18(1):734. doi: 10.1186/s12885-018-4656-3
  • Peisker A, Raschke GF, Fahmy MD, et al. Salivary MMP-9 in the detection of oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal. 2017;22(3):e270–275. doi: 10.4317/medoral.21626
  • Yu JS, Chen YT, Chiang WF, et al. Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan. Proc Natl Acad Sci USA. 2016;113(41):11549–11554. doi: 10.1073/pnas.1612368113
  • Metgud R, Bajaj S. Altered serum and salivary C-reactive protein levels in patients with oral premalignant lesions and oral squamous cell carcinoma. Biotechnic Histochem. 2016;91(2):96–101. doi: 10.3109/10520295.2015.1077393
  • Saluja TS, Spadigam A, Dhupar A, et al. Equating salivary lactate dehydrogenase (LDH) with LDH-5 expression in patients with oral squamous cell carcinoma: An insight into metabolic reprogramming of cancer cell as a predictor of aggressive phenotype. Tumour Biol. 2016;37(4):5609–5620. doi: 10.1007/s13277-015-4415-x
  • Giebultowicz J, Wroczynski P, Samolczyk-Wanyura D. Comparison of antioxidant enzymes activity and the concentration of uric acid in the saliva of patients with oral cavity cancer, odontogenic cysts and healthy subjects. J Pathology Med. 2011;40(9):726–730. doi: 10.1111/j.1600-0714.2011.01045.x
  • Brinkmann O, Kastratovic DA, Dimitrijevic MV, et al. Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population. Oral Oncol. 2011;47(1):51–55. doi: 10.1016/j.oraloncology.2010.10.009
  • Arellano-Garcia ME, Hu S, Wang J, et al. Multiplexed immunobead-based assay for detection of oral cancer protein biomarkers in saliva. Oral Dis. 2008;14(8):705–712. doi: 10.1111/j.1601-0825.2008.01488.x
  • Rhodus NL, Ho V, Miller CS, et al. NF-kappaB dependent cytokine levels in saliva of patients with oral preneoplastic lesions and oral squamous cell carcinoma. Cancer Detect Prev. 2005;29(1):42–45. doi: 10.1016/j.cdp.2004.10.003
  • Contucci AM, Inzitari R, Agostino S, et al. Statherin levels in saliva of patients with precancerous and cancerous lesions of the oral cavity: a preliminary report. Oral Dis. 2005;11(2):95–99. doi: 10.1111/j.1601-0825.2004.01057.x
  • Balicki R, Grabowska SZ, Citko A. Salivary epidermal growth factor in oral cavity cancer. Oral Oncol. 2005;41(1):48–55. doi: 10.1016/j.oraloncology.2004.06.004
  • Korostoff A, Reder L, Masood R, et al. The role of salivary cytokine biomarkers in tongue cancer invasion and mortality. Oral Oncol. 2011;47(4):282–287. doi: 10.1016/j.oraloncology.2011.02.006
  • Sivadasan P, Gupta MK, Sathe G, et al. Salivary proteins from dysplastic leukoplakia and oral squamous cell carcinoma and their potential for early detection. J Proteomics. 2020;212:103574. doi: 10.1016/j.jprot.2019.103574
  • Hsiao YC, Lin SY, Chien KY, et al. An immuno-MALDI mass spectrometry assay for the oral cancer biomarker, matrix metalloproteinase-1, in dried saliva spot samples. Anal Chim Acta. 2020;1100:118–130. doi: 10.1016/j.aca.2019.12.006
  • Ishikawa S, Ishizawa K, Tanaka A, et al. Identification of salivary proteomic biomarkers for oral cancer Screening. Vivo (Athens, Greece). 2021;35(1):541–547. doi: 10.21873/invivo.12289
  • Kang Y, Chen J, Li X, et al. Salivary KLK5 and uPA are potential biomarkers for malignant transformation of OLK and OLP. Cancer Biomark. 2021;31(4):317–328. doi: 10.3233/CBM-203105
  • Nakamichi E, Sakakura H, Mii S, et al. Detection of serum/salivary exosomal Alix in patients with oral squamous cell carcinoma. Oral Dis. 2021;27(3):439–447. doi: 10.1111/odi.13565
  • Babiuch K, Kusnierz-Cabala B, Kesek B, et al. Evaluation of Proinflammatory, NF-kappaB Dependent Cytokines: IL-1α, IL-6, IL-8, and TNF-α in Tissue specimens and saliva of patients with oral squamous cell carcinoma and oral potentially malignant disorders. J Clin Med. 2020;9(3):867. doi: 10.3390/jcm9030867
  • Zielinska K, Karczmarek-Borowska B, Kwasniak K, et al. Salivary IL-17A, IL-17F, and Tnf- α Are Associated with Disease Advancement in Patients with Oral and Oropharyngeal Cancer. J Immunol Res. 2020;2020:1–8. doi: 10.1155/2020/3928504
  • Rathore AS, Katyal S, Jain A, et al. Biochemical analysis of cytokeratin fragment 21-1 concentration and expression of cytokeratin 19 in oral potentially malignant disorders. J Cancer Res Ther. 2020;16(3):452–457. doi: 10.4103/jcrt.JCRT_893_17
  • Marton IJ, Horvath J, Labiscsak P, et al. Salivary IL-6 mRNA is a robust biomarker in oral squamous cell carcinoma. J Clin Med. 2019;8(11):1958. doi: 10.3390/jcm8111958
  • Lin YH, Eguez RV, Torralba MG, et al. Self-assembled strap for global proteomics and salivary biomarker discovery. J Proteome Res. 2019;18(4):1907–1915. doi: 10.1021/acs.jproteome.9b00037
  • Feng Y, Li Q, Chen J, et al. Salivary protease spectrum biomarkers of oral cancer. Int J Oral Sci. 2019;11(1):7. doi: 10.1038/s41368-018-0032-z
  • Janssen EM, Dy SM, Meara AS, et al. Analysis of patient preferences in lung cancer - estimating acceptable tradeoffs between treatment benefit and side effects. Patient Prefer Adherence. 2020;14:927–937. doi: 10.2147/PPA.S235430
  • Zheng J, Sun L, Yuan W, et al. Clinical value of Naa10p and CEA levels in saliva and serum for diagnosis of oral squamous cell carcinoma. J Oral Pathology Med. 2018;47(9):830–835. doi: 10.1111/jop.12767
  • Lopez-Verdin S, Soto-Avila JJ, Zamora-Perez AL, et al. Patients with advanced oral squamous cell carcinoma have high levels of soluble E-cadherin in the saliva. Med Oral Patol Oral Cir Bucal. 2017;22(6):e694–e701. doi: 10.4317/medoral.21907
  • Csosz E, Labiscsak P, Kallo G, et al. Proteomics investigation of OSCC-specific salivary biomarkers in a Hungarian population highlights the importance of identification of population-tailored biomarkers. PLOS ONE. 2017;12(5):e0177282. doi: 10.1371/journal.pone.0177282
  • Zanotti L, Paderno A, Piazza C, et al. Epidermal growth factor receptor detection in serum and saliva as a diagnostic and prognostic tool in oral cancer. Laryngoscope. 2017;127(11):E408–E414. doi: 10.1002/lary.26797
  • Ghallab NA, Shaker OG. Serum and salivary levels of chemerin and MMP-9 in oral squamous cell carcinoma and oral premalignant lesions. Clin Oral Investig. 2017;21(3):937–947. doi: 10.1007/s00784-016-1846-8
  • Honarmand MH, Farhad-Mollashahi L, Nakhaee A, et al. Salivary Levels of ErbB2 and CEA in oral squamous cell carcinoma patients. Asian Pac J Cancer Prev. 2016;17(S3):77–80. doi: 10.7314/APJCP.2016.17.S3.77
  • Malhotra R, Urs AB, Chakravarti A, et al. Correlation of Cyfra 21-1 levels in saliva and serum with CK19 mRNA expression in oral squamous cell carcinoma. Tumour Biol. 2016;37(7):9263–9271. doi: 10.1007/s13277-016-4809-4
  • Ajona D, Pajares MJ, Chiara MD, et al. Complement activation product C4d in oral and oropharyngeal squamous cell carcinoma. Oral Dis. 2015;21(7):899–904. doi: 10.1111/odi.12363
  • Winck FV, Prado Ribeiro AC, Ramos Domingues R, et al. Insights into immune responses in oral cancer through proteomic analysis of saliva and salivary extracellular vesicles. Sci Rep. 2015;5(1):16305. doi: 10.1038/srep16305
  • Rajkumar K, Ramya R, Nandhini G, et al. Salivary and serum level of CYFRA 21-1 in oral precancer and oral squamous cell carcinoma. Oral Dis. 2015;21(1):90–96. doi: 10.1111/odi.12216
  • Goncalves AS, Arantes DA, Bernardes VF, et al. Immunosuppressive mediators of oral squamous cell carcinoma in tumour samples and saliva. Hum Immunol. 2015;76(1):52–58. doi: 10.1016/j.humimm.2014.11.002
  • Patel S, Metgud R. Estimation of salivary lactate dehydrogenase in oral leukoplakia and oral squamous cell carcinoma: a biochemical study. J Cancer Res Ther. 2015;11(1):119–123. doi: 10.4103/0973-1482.138193
  • Varun C, Dineshkumar T, Jayant VS, et al. Salivary Her2/neu levels in differentiation of oral premalignant disorders and oral squamous cell carcinomas. Asian Pac J Cancer Prev. 2015;16(14):5773–5777. doi: 10.7314/APJCP.2015.16.14.5773
  • Arduino PG, Menegatti E, Cappello N, et al. Possible role for interleukins as biomarkers for mortality and recurrence in oral cancer. Int J Biol Markers. 2015;30(2):e262–266. doi: 10.5301/jbm.5000142
  • Hsu CW, Yu JS, Peng PH, et al. Secretome profiling of primary cells reveals that THBS2 is a salivary biomarker of oral cavity squamous cell carcinoma. J Proteome Res. 2014;13(11):4796–4807. doi: 10.1021/pr500038k
  • Jou YJ, Hua CH, Lin CD, et al. S100A8 as potential salivary biomarker of oral squamous cell carcinoma using nanoLC-MS/MS. Clin Chim Acta. 2014;436:121–129. doi: 10.1016/j.cca.2014.05.009
  • Mu AK, Chan YS, Kang SS, et al. Detection of host-specific immunogenic proteins in the saliva of patients with oral squamous cell carcinoma. J Immunoassay Immunochem. 2014;35(2):183–193. doi: 10.1080/15321819.2013.836535
  • Jessie K, Jayapalan JJ, Rahim ZH, et al. Aberrant proteins featured in the saliva of habitual betel quid chewers: an indication of early oral premalignancy? Electrophoresis. 2014;35(24):3504–3511. doi: 10.1002/elps.201400252
  • Chaiyarit P, Utrawichian A, Leelayuwat C, et al. Investigation of trefoil factor expression in saliva and oral mucosal tissues of patients with oral squamous cell carcinoma. Clin Oral Investig. 2012;16(6):1549–1556. doi: 10.1007/s00784-011-0667-z
  • Szanto I, Mark L, Bona A, et al. High-throughput screening of saliva for early detection of oral cancer: a pilot study. Technol Cancer Res Treat. 2012;11(2):181–188. doi: 10.7785/tcrt.2012.500248
  • Sartini D, Pozzi V, Renzi E, et al. Analysis of tissue and salivary nicotinamide N-methyltransferase in oral squamous cell carcinoma: basis for the development of a noninvasive diagnostic test for early-stage disease. Biol Chem. 2012;393(6):505–511. doi: 10.1515/hsz-2012-0112
  • Stott-Miller M, Houck JR, Lohavanichbutr P, et al. Tumor and salivary matrix metalloproteinase levels are strong diagnostic markers of oral squamous cell carcinoma. Cancer Epidemiol Biomarkers Preven. 2011;20(12):2628–2636. doi: 10.1158/1055-9965.EPI-11-0503
  • Jou YJ, Lin CD, Lai CH, et al. Salivary zinc finger protein 510 peptide as a novel biomarker for detection of oral squamous cell carcinoma in early stages. Clin Chim Acta. 2011;412(15–16):1357–1365. doi: 10.1016/j.cca.2011.04.004
  • Shintani S, Hamakawa H, Ueyama Y, et al. Identification of a truncated cystatin SA-I as a saliva biomarker for oral squamous cell carcinoma using the SELDI ProteinChip platform. Int J Oral Maxillofacial Surg. 2010;39(1):68–74. doi: 10.1016/j.ijom.2009.10.001
  • Hu S, Arellano M, Boontheung P, et al. Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res. 2008;14(19):6246–6252. doi: 10.1158/1078-0432.CCR-07-5037
  • Pickering V, Jordan RC, Schmidt BL. Elevated salivary endothelin levels in oral cancer patients–a pilot study. Oral Oncol. 2007;43(1):37–41. doi: 10.1016/j.oraloncology.2005.12.027
  • Zhong LP, Zhang CP, Zheng JW, et al. Increased Cyfra 21-1 concentration in saliva from primary oral squamous cell carcinoma patients. Arch Oral Biol. 2007;52(11):1079–1087. doi: 10.1016/j.archoralbio.2007.05.005
  • Rhodus NL, Cheng B, Myers S, et al. The feasibility of monitoring NF-kappaB associated cytokines: TNF-alpha, IL-1alpha, IL-6, and IL-8 in whole saliva for the malignant transformation of oral lichen planus. Mol Carcinog. 2005;44(2):77–82. doi: 10.1002/mc.20113
  • Xie H, Onsongo G, Popko J, et al. Proteomics analysis of cells in whole saliva from oral cancer patients via value-added three-dimensional peptide fractionation and tandem mass spectrometry. Mol Cell Proteomics. 2008;7(3):486–498. doi: 10.1074/mcp.M700146-MCP200
  • Xiao H, Zhang Y, Kim Y, et al. Differential proteomic analysis of human saliva using tandem Mass tags quantification for gastric cancer detection. Sci Rep. 2016;6(1):22165. doi: 10.1038/srep22165
  • Gold L, Ayers D, Bertino J, et al. Aptamer-based multiplexed proteomic technology for biomarker discovery. PLOS ONE. 2010;5(12):e15004. doi: 10.1371/journal.pone.0015004
  • Wang K, Shen Y, Xu J, et al. Evaluation of synuclein-gamma levels by novel monoclonal antibody in saliva and cancer tissues from oral squamous cell carcinoma patients. Neoplasma. 2020;67(3):707–713. doi: 10.4149/neo_2020_190619N523
  • Kawahara R, Bollinger JG, Rivera C, et al. A targeted proteomic strategy for the measurement of oral cancer candidate biomarkers in human saliva. Proteomics. 2016;16(1):159–173. doi: 10.1002/pmic.201500224
  • Nosratzehi F, Nosratzehi T, Alijani E, et al. Salivary beta2-microglobulin levels in patients with erosive oral lichen planus and squamous cell carcinoma. BMC Res Notes. 2020;13(1):294. doi: 10.1186/s13104-020-05135-w
  • Singh P, Verma JK, Singh JK. Validation of salivary markers, IL-1beta, IL-8 and Lgals3bp for detection of oral squamous cell carcinoma in an Indian population. Sci Rep. 2020;10(1):7365. doi: 10.1038/s41598-020-64494-3
  • Bernardes VF, Gleber-Netto FO, Sousa SF, et al. Clinical significance of EGFR, Her-2 and EGF in oral squamous cell carcinoma: a case control study. J Exp Clin Cancer Res. 2010;29(1):40. doi: 10.1186/1756-9966-29-40
  • Sabarathinam J, Selvaraj J, Devi S. Estimation of levels of glutathione peroxidase (gpx), malondialdehyde (mda), tumor necrosis factor alpha (Tnf Alpha) and alpha feto protein (Afp) in saliva of potentially malignant disorders and oral squamous cell carcinoma. Biomed Pharm J. 2019;12(4):1881–1886. doi: 10.13005/bpj/1818
  • Smriti K, Ray M, Chatterjee T, et al. Salivary MMP-9 as a biomarker for the diagnosis of oral potentially malignant disorders and oral squamous cell carcinoma. Asian Pac J Cancer Prev. 2020;21(1):233–238. doi: 10.31557/APJCP.2020.21.1.233
  • Csosz E, Markus B, Darula Z, et al. Salivary proteome profiling of oral squamous cell carcinoma in a Hungarian population. FEBS Open Bio. 2018;8(4):556–569. doi: 10.1002/2211-5463.12391
  • Cai M, Zheng Z, Bai Z, et al. Overexpression of angiogenic factors and matrix metalloproteinases in the saliva of oral squamous cell carcinoma patients: potential non-invasive diagnostic and therapeutic biomarkers. BMC Cancer. 2022;22(1):530. doi: 10.1186/s12885-022-09630-0
  • Geng XF, Du M, Han JX, et al. Saliva CA125 and TPS levels in patients with oral squamous cell carcinoma. Int J Biol Markers. 2013;28(2):216–220. doi: 10.5301/jbm.5000001
  • Lisa Cheng YS, Jordan L, Gorugantula LM, et al. Salivary interleukin-6 and -8 in patients with oral cancer and patients with chronic oral inflammatory diseases. J Periodontol. 2014;85(7):956–965. doi: 10.1902/jop.2013.130320
  • Vajaria BN, Patel KR, Begum R, et al. Salivary glyco-sialylation changes monitors oral carcinogenesis. Glycoconj J. 2014;31(9):649–659. doi: 10.1007/s10719-014-9561-7
  • Aziz S, Ahmed SS, Ali A, et al. Salivary Immunosuppressive Cytokines IL-10 and IL-13 are significantly elevated in oral squamous cell carcinoma patients. Cancer Invest. 2015;33(7):318–328. doi: 10.3109/07357907.2015.1041642
  • Krapfenbauer K, Drucker E, Thurnher D. Identification of tumour-related proteins as potential screening markers by proteome analysis-protein profiles of human saliva as a predictive and prognostic tool. EPMA Journal. 2014;5(1):20. doi: 10.1186/1878-5085-5-20
  • Li SX, Yang YQ, Jin LJ, et al. Detection of survivin, carcinoembryonic antigen and ErbB2 level in oral squamous cell carcinoma patients. Cancer Biomark. 2016;17(4):377–382. doi: 10.3233/CBM-160651
  • Chianeh YR, Manjunath R, Prabhu K, et al. Protein thiols and butyrylcholinesterase in saliva of oral cancer patients. Indian J Clin Biochem. 2014;29(2):238–241. doi: 10.1007/s12291-013-0352-x
  • Vajaria BN, Patel KR, Begum R, et al. Evaluation of serum and salivary total sialic acid and alpha-l-fucosidase in patients with oral precancerous conditions and oral cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115(6):764–771. doi: 10.1016/j.oooo.2013.01.004
  • Ko HH, Peng HH, Cheng SJ, et al. Increased salivary AKR1B10 level: association with progression and poor prognosis of oral squamous cell carcinoma. Head & Neck. 2018;40(12):2642–2647. doi: 10.1002/hed.25370
  • Seyedmajidi S, Seyedmajidi M, Foroughi R, et al. Comparison of salivary and serum soluble CD44 levels between patients with oral scc and healthy controls. Asian Pac J Cancer Prev. 2018;19(11):3059–3063. doi: 10.31557/APJCP.2018.19.11.3059
  • Heawchaiyaphum C, Pientong C, Phusingha P, et al. Peroxiredoxin-2 and zinc-alpha-2-glycoprotein as potentially combined novel salivary biomarkers for early detection of oral squamous cell carcinoma using proteomic approaches. J Proteomics. 2018;173:52–61. doi: 10.1016/j.jprot.2017.11.022
  • Jou YJ, Lin CD, Lai CH, et al. Proteomic identification of salivary transferrin as a biomarker for early detection of oral cancer. Anal Chim Acta. 2010;681(1–2):41–48. doi: 10.1016/j.aca.2010.09.030
  • Gholizadeh N, Mohebbi AH, Mirzaii-Dizgah I, et al. α1 adrenergic receptors in serum and saliva of patients with oral squamous cell carcinoma. Clin Transl Oncol. 2021;23(8):1705–1710. doi: 10.1007/s12094-021-02571-3
  • Shpitzer T, Hamzany Y, Bahar G, et al. Salivary analysis of oral cancer biomarkers. Br J Cancer. 2009;101(7):1194–1198. doi: 10.1038/sj.bjc.6605290
  • Gleber-Netto FO, Yakob M, Li F, et al. Salivary biomarkers for detection of oral squamous cell carcinoma in a Taiwanese population. Clin Cancer Res. 2016;22(13):3340–3347. doi: 10.1158/1078-0432.CCR-15-1761
  • Sato J, Ohuchi M, Abe K, et al. Correlation between salivary interleukin-6 levels and early locoregional recurrence in patients with oral squamous cell carcinoma: preliminary study. Head Neck. 2013;35(6):889–894. doi: 10.1002/hed.23056
  • Wu CC, Chang YT, Chang KP, et al. Salivary auto-antibodies as noninvasive diagnostic markers of oral cavity squamous cell carcinoma. Cancer Epidemiol Biomarker Prevent. 2014;23(8):1569–1578. doi: 10.1158/1055-9965.EPI-13-1269
  • Rai AK, Panda M, Das AK, et al. Dysbiosis of salivary microbiome and cytokines influence oral squamous cell carcinoma through inflammation. Arch Microbiol. 2021;203(1):137–152. doi: 10.1007/s00203-020-02011-w
  • Schork K, Podwojski K, Turewicz M, et al. Important issues in planning a proteomics experiment: statistical considerations of quantitative proteomic data. Methods Mol Biol. 2021;2228:1–20.
  • Voss H, Schlumbohm S, Barwikowski P, et al. HarmonizR enables data harmonization across independent proteomic datasets with appropriate handling of missing values. Nat Commun. 2022;13(1):3523. doi: 10.1038/s41467-022-31007-x
  • Wik L, Nordberg N, Broberg J, et al. Proximity extension assay in combination with next-generation sequencing for high-throughput proteome-wide analysis. Mol Cell Proteomics. 2021;20:100168. doi: 10.1016/j.mcpro.2021.100168
  • Kraemer S, Vaught JD, Bock C, et al. From SOMAmer-based biomarker discovery to diagnostic and clinical applications: a SOMAmer-based, streamlined multiplex proteomic assay. PLOS ONE. 2011;6(10):e26332. doi: 10.1371/journal.pone.0026332
  • Bourmaud A, Gallien S, Domon B. A quality control of proteomic experiments based on multiple isotopologous internal standards. EuPA Open Proteom. 2015;8:16–21. doi: 10.1016/j.euprot.2015.07.010
  • Zhou C, Simpson KL, Lancashire LJ, et al. Statistical considerations of optimal study design for human plasma proteomics and biomarker discovery. J Proteome Res. 2012;11(4):2103–2113. doi: 10.1021/pr200636x
  • Serdar CC, Cihan M, Yucel D, et al. Sample size, power and effect size revisited: simplified and practical approaches in pre-clinical, clinical and laboratory studies. Biochem med (Online). 2021;31(1):27–53. doi: 10.11613/BM.2021.010502
  • Hajian-Tilaki K. Sample size estimation in diagnostic test studies of biomedical informatics. J Biomed Informat. 2014;48:193–204. doi: 10.1016/j.jbi.2014.02.013
  • Andrade C. Sample size and its importance in research. Indian J Psychol Med. 2020;42(1):102–103. doi: 10.4103/IJPSYM.IJPSYM_504_19
  • Gumpili SP, Das AV. Sample size and its evolution in research. IHOPE Journal Of Ophthalmology. 2022;1:9–13. doi: 10.25259/IHOPEJO_3_2021
  • Magaki S, Hojat SA, Wei B, et al. An Introduction to the Performance of Immunohistochemistry. Methods Mol Biol. 2019;1897:289–298.
  • Matos LL, Trufelli DC, de Matos MG, et al. Immunohistochemistry as an important tool in biomarkers detection and clinical practice. Biomark Insights. 2010;5:9–20. doi: 10.4137/BMI.S2185
  • Gupta R, Kurc T, Sharma A, et al. The emergence of Pathomics. Curr Pathobiol Rep. 2019;7(3):73–84. doi: 10.1007/s40139-019-00200-x
  • Bankhead P, Loughrey MB, Fernandez JA, et al. QuPath: open source software for digital pathology image analysis. Sci Rep. 2017;7(1):16878. doi: 10.1038/s41598-017-17204-5
  • Normando AGC, Dos Santos ES, Sa JO, et al. A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia. Front Oral Health. 2023;4:1088022. doi: 10.3389/froh.2023.1088022
  • Arroyo E, Donis SP, Petronacci CMC, et al. Usefulness of protein-based salivary markers in the diagnosis of oral potentially malignant disorders: A systematic review and meta-analysis. Cancer Biomark. 2021;32(4):411–424. doi: 10.3233/CBM-203043
  • Piyarathne NS, Rasnayake R, Angammana R, et al. Diagnostic salivary biomarkers in oral cancer and oral potentially malignant disorders and their relationships to risk factors - a systematic review. Expert Rev Mol Diagn. 2021;21(8):789–807. doi: 10.1080/14737159.2021.1944106
  • Chiamulera MMA, Zancan CB, Remor AP, et al. Salivary cytokines as biomarkers of oral cancer: a systematic review and meta-analysis. BMC Cancer. 2021;21(1):205. doi: 10.1186/s12885-021-07932-3
  • Iglesias-Velazquez O, Lopez-Pintor RM, Gonzalez-Serrano J, et al. Salivary LDH in oral cancer and potentially malignant disorders: a systematic review and meta-analysis. Oral Dis. 2022;28(1):44–56. doi: 10.1111/odi.13630
  • Sa JO, Trino LD, Oliveira AK, et al. Proteomic approaches to assist in diagnosis and prognosis of oral cancer. Expert Rev Proteomics. 2021;18(4):261–284. doi: 10.1080/14789450.2021.1924685
  • Amenabar JM, Da Silva BM, Punyadeera C. Salivary protein biomarkers for head and neck cancer. Expert Rev Mol Diagn. 2020;20(3):305–313. doi: 10.1080/14737159.2020.1722102
  • Benito-Ramal E, Egido-Moreno S, Gonzalez-Navarro B, et al. Role of selected salivary inflammatory cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. A systematic review and meta-analysis. Med Oral Patol Oral Cir Bucal. 2023;28(5):e474–e486. doi: 10.4317/medoral.25889
  • Hema Shree K, Ramani P, Sherlin H, et al. Saliva as a diagnostic tool in oral squamous cell carcinoma – a systematic review with meta analysis. Pathol Oncol Res. 2019;25(2):447–453. doi: 10.1007/s12253-019-00588-2
  • AlAli AM, Walsh T, Maranzano M. CYFRA 21-1 and MMP-9 as salivary biomarkers for the detection of oral squamous cell carcinoma: a systematic review of diagnostic test accuracy. Int J Oral Maxillofacial Surg. 2020;49(8):973–983. doi: 10.1016/j.ijom.2020.01.020