Salivary Biomarkers for Prostate Cancer: A Case-Control Study of PSA and S100P in Iranian
Abstract
Objectives: Early detection of prostate disease is crucial, but current methods have limitations. S100P protein and saliva sampling offer potential non-invasive diagnostic options. This study aimed to evaluate S100P and PSA as biomarkers for prostate cancer (PC) and differentiate PC from benign prostatic hyperplasia (BPH). Additionally, the study investigated the suitability of saliva as a diagnostic medium for prostate patients.
Methods: This case-control study included 100 Iranian men aged 50 to 65 years, divided into two groups: 50 men with PC and 50 men with BPH. Serum and saliva samples were collected from each patient after a consent form was obtained. Serum and salivary PSA and S100P levels were measured using ELISA kits. Mann–Whitney U test, Spearman’s correlation coefficients and receiver operating characteristic (ROC) analysis were applied to evaluate the data.
Results: Salivary and serum PSA and S100P levels were significantly higher in men with PC compared to those with BPH (P<0.001). A strong positive correlation was observed between serum and salivary levels of both biomarkers in two groups (P<0.001). ROC curve analysis indicated that salivary PSA and S100P levels could effectively differentiate PC from BPH.
Conclusions: Salivary PSA and S100P hold promise as non-invasive biomarkers for PC detection and differentiation from BPH. Further research with larger cohorts is needed to validate these findings and confirm the clinical utility of salivary PSA and S100P in PC and BPH diagnosis and management.
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2. Lin J, Nousome D, Jiang J, Chesnut GT, Shriver CD, Zhu K. Five-year survival of patients with late-stage prostate cancer: comparison of the Military Health System and the U.S. general population. British journal of cancer. 2023 Apr;128(6):1070-6. PubMed PMID: 36609596. Pubmed Central PMCID: PMC10006403. Epub 2023/01/08. eng.
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4. Tidd-Johnson A, Sebastian SA, Co EL, Afaq M, Kochhar H, Sheikh M, et al. Prostate cancer screening: Continued controversies and novel biomarker advancements. Current urology. 2022 Dec;16(4):197-206. PubMed PMID: 36714234. Pubmed Central PMCID: PMC9875204. Epub 2023/01/31. eng.
5. Yin F, He Q-D, Chen J, Gui T-J, Cai R-J, Wang Y, et al. Benign prostatic hyperplasia associated with white matter hyperintensities in men. Clinical Neurology and Neurosurgery. 2023 2023/06/01/;229:107738.
6. Medina JJ, Parra RO, Moore RG. BENIGN PROSTATIC HYPERPLASIA (THE AGING PROSTATE). Medical Clinics of North America. 1999 1999/09/01/;83(5):1213-29.
7. Jedinak A, Curatolo A, Zurakowski D, Dillon S, Bhasin MK, Libermann TA, et al. Novel non-invasive biomarkers that distinguish between benign prostate hyperplasia and prostate cancer. BMC cancer. 2015 Apr 11;15:259. PubMed PMID: 25884438. Pubmed Central PMCID: PMC4433087. Epub 2015/04/18. eng.
8. Gibadulinova A, Pastorek M, Filipcik P, Radvak P, Csaderova L, Vojtesek B, et al. Cancer-associated S100P protein binds and inactivates p53, permits therapy-induced senescence and supports chemoresistance. Oncotarget. 2016 Apr 19;7(16):22508-22. PubMed PMID: 26967060. Pubmed Central PMCID: PMC5008377. Epub 2016/03/12. eng.
9. Arumugam T, Logsdon CD. S100P: a novel therapeutic target for cancer. Amino acids. 2011 Oct;41(4):893-9. PubMed PMID: 20509035. Pubmed Central PMCID: PMC4041611. Epub 2010/05/29. eng.
10. Arumugam T, Simeone DM, Schmidt AM, Logsdon CD. S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). The Journal of biological chemistry. 2004 Feb 13;279(7):5059-65. PubMed PMID: 14617629. Epub 2003/11/18. eng.
11. Mercado-Pimentel ME, Onyeagucha BC, Li Q, Pimentel AC, Jandova J, Nelson MA. The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells. FEBS letters. 2015 Aug 19;589(18):2388-93. PubMed PMID: 26193421. Pubmed Central PMCID: PMC4582666. Epub 2015/07/21. eng.
12. Liu Y, Wang C, Shan X, Wu J, Liu H, Liu H, et al. S100P is associated with proliferation and migration in nasopharyngeal carcinoma. Oncology letters. 2017;14(1):525-32.
13. Senevirathna K, Mahakapuge TAN, Jayawardana NU, Rajapakse J, Gamage CU, Seneviratne B, et al. Diagnostic potential of salivary IL-1β, IL-8, SAT, S100P, and OAZ1 in oral squamous cell carcinoma, oral submucous fibrosis, and oral lichen planus based on findings from a Sri Lankan cohort. Scientific reports. 2024 Nov 8;14(1):27226. PubMed PMID: 39516476. Pubmed Central PMCID: PMC11549458. Epub 2024/11/13. eng.
14. 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. Translational Oncology. 2024 2024/02/01/;40:101827.
15. Pittman TW, Decsi DB, Punyadeera C, Henry CS. Saliva-based microfluidic point-of-care diagnostic. Theranostics. 2023;13(3):1091-108. PubMed PMID: 36793864. Pubmed Central PMCID: PMC9925318. Epub 2023/02/17. eng.
16. Liao C, Chen X, Fu Y. Salivary analysis: An emerging paradigm for non-invasive healthcare diagnosis and monitoring. Interdisciplinary Medicine. 2023;1(3):e20230009.
17. Okuyama K, Yanamoto S. Saliva in Balancing Oral and Systemic Health, Oral Cancer, and Beyond: A Narrative Review. Cancers. 2024;16(24):4276. PubMed PMID: doi:10.3390/cancers16244276.
18. Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ, et al. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. Journal of Clinical Oncology. 2015;33(30):3379.
19. Rapado-González Ó, Majem B, Muinelo-Romay L, López-López R, Suarez-Cunqueiro MM. Cancer salivary biomarkers for tumours distant to the oral cavity. International journal of molecular sciences. 2016;17(9):1531.
20. Cui Y, Yang M, Zhu J, Zhang H, Duan Z, Wang S, et al. Developments in diagnostic applications of saliva in human organ diseases. Medicine in Novel Technology and Devices. 2022 2022/03/01/;13:100115.
21. Zhang CZ, Cheng XQ, Li JY, Zhang P, Yi P, Xu X, et al. Saliva in the diagnosis of diseases. International journal of oral science. 2016 Sep 29;8(3):133-7. PubMed PMID: 27585820. Pubmed Central PMCID: PMC5113094. Epub 2016/09/03. eng.
22. Filella X, Foj L. Prostate cancer detection and prognosis: from prostate specific antigen (PSA) to exosomal biomarkers. International journal of molecular sciences. 2016;17(11):1784.
23. Usoro AJ, Obot AS, Ekaidem IS, Akaiso OE, Udoh AE, Akinloye O. Serum testosterone, 17β-estradiol and PSA levels in subjects with prostate disorders. Indian Journal of Clinical Biochemistry. 2015;30(1):59-65.
24. Siemińska L, Borowski A, Marek B, Nowak M, Kajdaniuk D, Warakomski J, et al. Serum concentrations of adipokines in men with prostate cancer and benign prostate hyperplasia. Endokrynologia Polska. 2018;69(2):120-7.
25. Reshma K, Kuthethur S, Manjerekar P, Gopal M. Evaluation of biochemical markers of renal dysfunction in prostate disorders and healthy controls. Int J Biochem Adv Res. 2014;5(9).
26. Farahani H, Alaee M, Amri J, Baghinia M-R, Rafiee M. Serum and saliva concentrations of biochemical parameters in men with prostate cancer and benign prostate hyperplasia. Laboratory medicine. 2020;51(3):243-51.
27. Shiiki N, Tokuyama S, Sato C, Kondo Y, Saruta J, Mori Y, et al. Association between saliva PSA and serum PSA in conditions with prostate adenocarcinoma. Biomarkers. 2011;16(6):498-503.
28. Ayatollahi H, Mahboub MRD, Mohammadian N, Parizadeh MR, Kianoosh T, Khoob MK, et al. Ratios of free to total prostate-specific antigen and total prostate specific antigen to protein concentrations in saliva and serum of healthy men. Urology journal. 2009;4(4):238-41.
29. Turan T, Demir S, Aybek H, Atahan O, Tuncay OL, Aybek Z. Free and Total Prostate–Specific Antigen Levels in Saliva and the Comparison with Serum Levels in Men. European urology. 2000;38(5):550-4.
30. Sato N, Hitomi J. S100P expression in human esophageal epithelial cells: Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation. The Anatomical Record: An Official Publication of the American Association of Anatomists. 2002;267(1):60-9.
31. Basu GD, Azorsa DO, Kiefer JA, Rojas AM, Tuzmen S, Barrett MT, et al. Functional evidence implicating S100P in prostate cancer progression. International journal of cancer. 2008;123(2):330-9.
32. Lee S-H, Park NR, Park EK, Kim J-E. S100P binds to RAGE and activates ERK/NF-κB signaling to promote osteoclast differentiation and activity. Biochemical and Biophysical Research Communications. 2024 2024/12/17/;738:150536.
33. Arumugam T, Simeone DM, Schmidt AM, Logsdon CD. S100P Stimulates Cell Proliferation and Survival via Receptor for Activated Glycation End Products (RAGE)*. Journal of Biological Chemistry. 2004 2004/02/13/;279(7):5059-65.
34. Wu Z, Boonmars T, Nagano I, Boonjaraspinyo S, Srinontong P, Ratasuwan P, et al. Significance of S100P as a biomarker in diagnosis, prognosis and therapy of opisthorchiasis‐associated cholangiocarcinoma. International Journal of Cancer. 2016;138(2):396-408.
35. Wang Q, Zhang Y-N, Lin G-L, Qiu H-Z, Wu B, Wu H-Y, et al. S100P, a potential novel prognostic marker in colorectal cancer. Oncology reports. 2012;28(1):303-10.
2. Lin J, Nousome D, Jiang J, Chesnut GT, Shriver CD, Zhu K. Five-year survival of patients with late-stage prostate cancer: comparison of the Military Health System and the U.S. general population. British journal of cancer. 2023 Apr;128(6):1070-6. PubMed PMID: 36609596. Pubmed Central PMCID: PMC10006403. Epub 2023/01/08. eng.
3. Prostate Cancer Screening (PDQ®): Patient Version. PDQ Cancer Information Summaries. Bethesda MD2002.
4. Tidd-Johnson A, Sebastian SA, Co EL, Afaq M, Kochhar H, Sheikh M, et al. Prostate cancer screening: Continued controversies and novel biomarker advancements. Current urology. 2022 Dec;16(4):197-206. PubMed PMID: 36714234. Pubmed Central PMCID: PMC9875204. Epub 2023/01/31. eng.
5. Yin F, He Q-D, Chen J, Gui T-J, Cai R-J, Wang Y, et al. Benign prostatic hyperplasia associated with white matter hyperintensities in men. Clinical Neurology and Neurosurgery. 2023 2023/06/01/;229:107738.
6. Medina JJ, Parra RO, Moore RG. BENIGN PROSTATIC HYPERPLASIA (THE AGING PROSTATE). Medical Clinics of North America. 1999 1999/09/01/;83(5):1213-29.
7. Jedinak A, Curatolo A, Zurakowski D, Dillon S, Bhasin MK, Libermann TA, et al. Novel non-invasive biomarkers that distinguish between benign prostate hyperplasia and prostate cancer. BMC cancer. 2015 Apr 11;15:259. PubMed PMID: 25884438. Pubmed Central PMCID: PMC4433087. Epub 2015/04/18. eng.
8. Gibadulinova A, Pastorek M, Filipcik P, Radvak P, Csaderova L, Vojtesek B, et al. Cancer-associated S100P protein binds and inactivates p53, permits therapy-induced senescence and supports chemoresistance. Oncotarget. 2016 Apr 19;7(16):22508-22. PubMed PMID: 26967060. Pubmed Central PMCID: PMC5008377. Epub 2016/03/12. eng.
9. Arumugam T, Logsdon CD. S100P: a novel therapeutic target for cancer. Amino acids. 2011 Oct;41(4):893-9. PubMed PMID: 20509035. Pubmed Central PMCID: PMC4041611. Epub 2010/05/29. eng.
10. Arumugam T, Simeone DM, Schmidt AM, Logsdon CD. S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). The Journal of biological chemistry. 2004 Feb 13;279(7):5059-65. PubMed PMID: 14617629. Epub 2003/11/18. eng.
11. Mercado-Pimentel ME, Onyeagucha BC, Li Q, Pimentel AC, Jandova J, Nelson MA. The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells. FEBS letters. 2015 Aug 19;589(18):2388-93. PubMed PMID: 26193421. Pubmed Central PMCID: PMC4582666. Epub 2015/07/21. eng.
12. Liu Y, Wang C, Shan X, Wu J, Liu H, Liu H, et al. S100P is associated with proliferation and migration in nasopharyngeal carcinoma. Oncology letters. 2017;14(1):525-32.
13. Senevirathna K, Mahakapuge TAN, Jayawardana NU, Rajapakse J, Gamage CU, Seneviratne B, et al. Diagnostic potential of salivary IL-1β, IL-8, SAT, S100P, and OAZ1 in oral squamous cell carcinoma, oral submucous fibrosis, and oral lichen planus based on findings from a Sri Lankan cohort. Scientific reports. 2024 Nov 8;14(1):27226. PubMed PMID: 39516476. Pubmed Central PMCID: PMC11549458. Epub 2024/11/13. eng.
14. 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. Translational Oncology. 2024 2024/02/01/;40:101827.
15. Pittman TW, Decsi DB, Punyadeera C, Henry CS. Saliva-based microfluidic point-of-care diagnostic. Theranostics. 2023;13(3):1091-108. PubMed PMID: 36793864. Pubmed Central PMCID: PMC9925318. Epub 2023/02/17. eng.
16. Liao C, Chen X, Fu Y. Salivary analysis: An emerging paradigm for non-invasive healthcare diagnosis and monitoring. Interdisciplinary Medicine. 2023;1(3):e20230009.
17. Okuyama K, Yanamoto S. Saliva in Balancing Oral and Systemic Health, Oral Cancer, and Beyond: A Narrative Review. Cancers. 2024;16(24):4276. PubMed PMID: doi:10.3390/cancers16244276.
18. Tosoian JJ, Mamawala M, Epstein JI, Landis P, Wolf S, Trock BJ, et al. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. Journal of Clinical Oncology. 2015;33(30):3379.
19. Rapado-González Ó, Majem B, Muinelo-Romay L, López-López R, Suarez-Cunqueiro MM. Cancer salivary biomarkers for tumours distant to the oral cavity. International journal of molecular sciences. 2016;17(9):1531.
20. Cui Y, Yang M, Zhu J, Zhang H, Duan Z, Wang S, et al. Developments in diagnostic applications of saliva in human organ diseases. Medicine in Novel Technology and Devices. 2022 2022/03/01/;13:100115.
21. Zhang CZ, Cheng XQ, Li JY, Zhang P, Yi P, Xu X, et al. Saliva in the diagnosis of diseases. International journal of oral science. 2016 Sep 29;8(3):133-7. PubMed PMID: 27585820. Pubmed Central PMCID: PMC5113094. Epub 2016/09/03. eng.
22. Filella X, Foj L. Prostate cancer detection and prognosis: from prostate specific antigen (PSA) to exosomal biomarkers. International journal of molecular sciences. 2016;17(11):1784.
23. Usoro AJ, Obot AS, Ekaidem IS, Akaiso OE, Udoh AE, Akinloye O. Serum testosterone, 17β-estradiol and PSA levels in subjects with prostate disorders. Indian Journal of Clinical Biochemistry. 2015;30(1):59-65.
24. Siemińska L, Borowski A, Marek B, Nowak M, Kajdaniuk D, Warakomski J, et al. Serum concentrations of adipokines in men with prostate cancer and benign prostate hyperplasia. Endokrynologia Polska. 2018;69(2):120-7.
25. Reshma K, Kuthethur S, Manjerekar P, Gopal M. Evaluation of biochemical markers of renal dysfunction in prostate disorders and healthy controls. Int J Biochem Adv Res. 2014;5(9).
26. Farahani H, Alaee M, Amri J, Baghinia M-R, Rafiee M. Serum and saliva concentrations of biochemical parameters in men with prostate cancer and benign prostate hyperplasia. Laboratory medicine. 2020;51(3):243-51.
27. Shiiki N, Tokuyama S, Sato C, Kondo Y, Saruta J, Mori Y, et al. Association between saliva PSA and serum PSA in conditions with prostate adenocarcinoma. Biomarkers. 2011;16(6):498-503.
28. Ayatollahi H, Mahboub MRD, Mohammadian N, Parizadeh MR, Kianoosh T, Khoob MK, et al. Ratios of free to total prostate-specific antigen and total prostate specific antigen to protein concentrations in saliva and serum of healthy men. Urology journal. 2009;4(4):238-41.
29. Turan T, Demir S, Aybek H, Atahan O, Tuncay OL, Aybek Z. Free and Total Prostate–Specific Antigen Levels in Saliva and the Comparison with Serum Levels in Men. European urology. 2000;38(5):550-4.
30. Sato N, Hitomi J. S100P expression in human esophageal epithelial cells: Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation. The Anatomical Record: An Official Publication of the American Association of Anatomists. 2002;267(1):60-9.
31. Basu GD, Azorsa DO, Kiefer JA, Rojas AM, Tuzmen S, Barrett MT, et al. Functional evidence implicating S100P in prostate cancer progression. International journal of cancer. 2008;123(2):330-9.
32. Lee S-H, Park NR, Park EK, Kim J-E. S100P binds to RAGE and activates ERK/NF-κB signaling to promote osteoclast differentiation and activity. Biochemical and Biophysical Research Communications. 2024 2024/12/17/;738:150536.
33. Arumugam T, Simeone DM, Schmidt AM, Logsdon CD. S100P Stimulates Cell Proliferation and Survival via Receptor for Activated Glycation End Products (RAGE)*. Journal of Biological Chemistry. 2004 2004/02/13/;279(7):5059-65.
34. Wu Z, Boonmars T, Nagano I, Boonjaraspinyo S, Srinontong P, Ratasuwan P, et al. Significance of S100P as a biomarker in diagnosis, prognosis and therapy of opisthorchiasis‐associated cholangiocarcinoma. International Journal of Cancer. 2016;138(2):396-408.
35. Wang Q, Zhang Y-N, Lin G-L, Qiu H-Z, Wu B, Wu H-Y, et al. S100P, a potential novel prognostic marker in colorectal cancer. Oncology reports. 2012;28(1):303-10.
| Files | ||
| Issue | Vol 2 No 3 (2024) | |
| Section | Original Articles | |
| Keywords | ||
| Prostate cancer benign prostatic hyperplasia S100P Saliva | ||
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How to Cite
1.
Amri J, Goodarzi D, Alaee M, Zarei M, Salehi M. Salivary Biomarkers for Prostate Cancer: A Case-Control Study of PSA and S100P in Iranian. ABI. 2024;2(3):132-138.
