Salivary Lactate Dehydrogenase and Matrix Metalloproteinase-9 as Potential Diagnostic Markers for Oral Squamous Cell Carcinoma

Alyaa Jabbar Qasim; Ashjan Mohammed Hussein; Tareq Hafdi Abdtawfeeq; Zinah Ameer Abbood

doi:10.54133/ajms.v8i2.1681

Authors

Alyaa Jabbar Qasim Iraqi Center of Cancer and Medical Genetic Research, Mustansiriyah University, Baghdad, Iraq
Ashjan Mohammed Hussein Iraqi Center of Cancer and Medical Genetic Research, Mustansiriyah University, Baghdad, Iraq
Tareq Hafdi Abdtawfeeq Department of Medical Techniques, Al-Farahidi University, Baghdad, Iraq
Zinah Ameer Abbood Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq

DOI:

https://doi.org/10.54133/ajms.v8i2.1681

Keywords:

Lactate dehydrogenase, Matrix matalloproteinase, Oral squamous cell carcinoma, Saliva

Abstract

Background: Saliva is probably the most attractive secretion for the finding of biomarkers for OSCC, as its collection is easy, non-invasive, fast, and cost-effective Objective: The aim of this study was to exam increased salivary levels of lactate dehydrogenase (LDH) and Matrix Metalloproteinase-9 (MMP -9) that have been assessed as possible biomarkers for the diagnosis of oral squamous cell carcinoma (OSCC). Methods: Participants were divided into 30 (15 male and 15 female) of healthy controls, and 65 (45 male 20 female) patients were diagnosed with OSCC. The salivary levels of both LDH and MMP-9 were spectrophotometrically measured using standard LDH and MMP-9 kits. One-way ANOVA, Chi-square test, Pearson’s correlation test was applied to analyze the data. Results: The salivary levels of LDH and MMP-9 in OSCC patients were significantly higher than that the control groups. Significant associations were noted between LDH and MMP-9 salivary levels. Conclusions: Patients with OSCC had higher saliva levels of both LDH and MMP-9 than control groups.

Downloads

Download data is not yet available.

References

Gualtero DF, Suarez Castillo A. Biomarkers in saliva for the detection of oral squamous cell carcinoma and their potential use for early diagnosis: a systematic review. Acta Odontol Scand. 2016;74(3):170-177. doi: 10.3109/00016357.2015.1110249. DOI: https://doi.org/10.3109/00016357.2015.1110249

Harada H, Kikuchi M, Asato R, Hamaguchi K, Tamaki H, Mizuta M, et al. Characteristics of oral squamous cell carcinoma focusing on cases unaffected by smoking and drinking: A multicenter retrospective study. Head Neck. 2023;45(7):1812-1822. doi: 10.1002/hed.27398. DOI: https://doi.org/10.1002/hed.27398

Nguyen TTH, Sodnom-Ish B, Choi SW, Jung HI, Cho J, Hwang I, et al. Salivary biomarkers in oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg. 2020;46(5):301-312. doi: 10.5125/jkaoms.2020.46.5.301. DOI: https://doi.org/10.5125/jkaoms.2020.46.5.301

Joshi PS, Chougule M, Dudanakar M, Golgire S. Comparison between salivary and serum lactate dehydrogenase levels in patients with oral leukoplakia and oral squamous cell carcinoma--a pilot study. Int J Oral Maxillofac Pathol. 2012;3(4):1-7.

Long G, Tang W, Fu X, Liu D, Zhang L, Hu G, et al. Pre-treatment serum lactate dehydrogenase predicts distant metastasis and poor survival in nasopharyngeal carcinoma. J Cancer. 2019; 10(16):3657-3664. doi:10.7150/jca.32716. DOI: https://doi.org/10.7150/jca.32716

Mcparland H. Oral lichenoid and lichen planus-like lesions. Prim Dent J. 2016;5(1):34–39. DOI: https://doi.org/10.1177/205016841600500103

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. DOI: https://doi.org/10.4103/0973-1482.138193

Tang P, Xu J, Oliveira CL, Li ZJ, Liu SA. Mechanistic kinetic description of lactate dehydrogenase elucidating cancer diagnosis and inhibitor evaluation. J Enzyme Inhib Med Chem. 2017;32(1):564-571. doi: 10.1080/14756366.2016.1275606. DOI: https://doi.org/10.1080/14756366.2016.1275606

Hu CC, Wang SG, Gao Z, Qing MF, Pan S, Liu YY, et al. Emerging salivary biomarkers for early detection of oral squamous cell carcinoma. World J Clin Oncol. 2025;16(4):103803 doi: 10.5306/wjco.v16.i4.103803. DOI: https://doi.org/10.5306/wjco.v16.i4.103803

Javaraiah RK, David CM, Namitha J, Tiwari R, Benakanal P. Evaluation of salivary lactate dehydrogenase as a prognostic biomarker in tobacco users with and without potentially malignant disorders of the oral cavity. South Asian J Cancer. 2020;9(2):93-98. doi: 10.1055/s-0040-1721. DOI: https://doi.org/10.1055/s-0040-1721174

Huang H. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances. Sensors (Basel). 2018;18(10):3249. doi: 10.3390/s18103249. DOI: https://doi.org/10.3390/s18103249

Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, et al. The Roles of matrix metalloproteinases and their inhibitors in human diseases. Int J Mol Sci. 2020;21(24):9739. doi: 10.3390/ijms21249739. DOI: https://doi.org/10.3390/ijms21249739

Molière S, Jaulin A, Tomasetto CL, Dali-Youcef N. Roles of matrix metalloproteinases and their natural inhibitors in metabolism: Insights into health and disease. Int J Mol Sci. 2023; 24(13):10649. doi: 10.3390/ijms241310649. DOI: https://doi.org/10.3390/ijms241310649

Cui N, Hu M, Khalil RA. Biochemical and biological attributes of matrix metalloproteinases. Prog Mol Biol Transl Sci. 2017;147:1-73. doi: 10.1016/bs.pmbts.2017.02.005. DOI: https://doi.org/10.1016/bs.pmbts.2017.02.005

van der Meij EH, van der Waal I. Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications. J Oral Pathol Med. 2003;32(9):507-512. doi: 10.1034/j.1600-0714.2003.00125.x. DOI: https://doi.org/10.1034/j.1600-0714.2003.00125.x

Kallalli BN, Rawson K, Singh A, Awati MA, Shivhare P. Lactate dehydrogenase as a biomarker in oral cancer and oral submucous fibrosis. J Oral Pathol Med. 2016;45(9):687–690. DOI: https://doi.org/10.1111/jop.12451

Lokesh K, Kannabiran J, Rao MD. Salivary Lactate Dehydrogenase (LDH)- A Novel Technique in Oral Cancer Detection and Diagnosis. J Clin Diagn Res. 2016;10(2):34-37. doi: 10.7860/JCDR/2016/16243.7223. DOI: https://doi.org/10.7860/JCDR/2016/16243.7223

Forkasiewicz A, Dorociak M, Stach K, Szelachowski P, Tabola R, Augoff K. The usefulness of lactate dehydrogenase measurements in current oncological practice. Cell Mol Biol Lett. 2020;25:35. doi: 10.1186/s11658-020-00228-7. DOI: https://doi.org/10.1186/s11658-020-00228-7

Mahapatra M, Panda A, Kumar H, Barman D, Talukdar R, Dakshinakabat P. Lactate dehydrogenase as a biomarker in oral submucous fibrosis: A systematic review and meta-analysis. Cureus. 2023;15(12):51008. doi: 10.7759/cureus.51008. DOI: https://doi.org/10.7759/cureus.51008

Joshi PS, Golgire S. A study of salivary lactate dehydrogenase isoenzyme levels in patients with oral leukoplakia and squamous cell carcinoma by gel electrophoresis method. J Oral Maxillofac Pathol. 2014;18(Suppl 1):39-44. doi: 10.4103/0973-029X.141342. DOI: https://doi.org/10.4103/0973-029X.141342

Goyal G. Comparison of salivary and serum alkaline phosphates level and lactate dehydrogenase levels in patients with tobacco related oral lesions with healthy subjects - A step towards early diagnosis. Asian Pac J Cancer Prev. 2020;21(4):983-991. doi: 10.31557/APJCP.2020.21.4.983. DOI: https://doi.org/10.31557/APJCP.2020.21.4.983

Zhou Y, Tao L, Qiu J, Xu J, Yang X, Zhang Y, et al. Tumor biomarkers for diagnosis, prognosis and targeted therapy. Signal Transduct Target Ther. 2024;9(1):132. doi: 10.1038/s41392-024-01823-2. DOI: https://doi.org/10.1038/s41392-024-01823-2

Pereira T, Shetty S, Pereira S. Estimation of serum lactate dehydrogenase level in patients with oral premalignant lesions/conditions and oral squamous cell carcinoma: a clinicopathological study. J Cancer Res Ther. 2015;11(1):78-82. doi: 10.4103/0973-1482.150352. DOI: https://doi.org/10.4103/0973-1482.150352

Shpitzer T, Bahar G, Feinmesser R, Nagler RM. A comprehensive salivary analysis for oral cancer diagnosis. J Cancer Res Clin Oncol. 2007;133(9):613-617. doi: 10.1007/s00432-007-0207-z. DOI: https://doi.org/10.1007/s00432-007-0207-z

Samlin SS, Divya K, Siva B, Sudarshan R, Vignesswary A, Kumar MR. Salivary lactate dehydrogenasea biomarker of potentially malignant and malignant diseases of oral cavity? Asian J Dent Sci. 2020;2(1): 64-69.

Shetty SR, Chadha R, Babu S, Kumari S, Bhat S, Achalli S. Salivary lactate dehydrogenase levels in oral leukoplakia and oral squamous cell carcinoma: a biochemical and clinicopathological study. J Cancer Res Ther. 2012;8 Suppl 1:S123-125. doi: 10.4103/0973-1482.92226. DOI: https://doi.org/10.4103/0973-1482.92226

Sivaramakrishnan M, Sivapathasundharam B, Jananni M. Evaluation of lactate dehydrogenase enzyme activity in saliva and serum of oral sub mucous fibrosis patients. J Oral Pathol Med. 2015;44(6):449–452. doi: 10.1111/jop.12246. DOI: https://doi.org/10.1111/jop.12246

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. DOI: https://doi.org/10.1007/s00784-016-1846-8

Rao K, Babu SG, Kumari S. Estimation of serum and salivary lactate dehydrogenase levels among healthy individuals and oral cancer patients—a clinical and biochemical study. Int J Dent Res. 2017;2(2):31–35. doi: 10.31254/dentistry.2017.2203. DOI: https://doi.org/10.31254/dentistry.2017.2203

Gholizadeh N, Ramandi M, Motiee-Langroudi M, Jafari M, Sharouny H, Sheykhbahaei N. Serum and salivary levels of lactate dehydrogenase in oral squamous cell carcinoma, oral lichen planus and oral lichenoid reaction. BMC Oral Health. 2020;20(1):314. doi: 10.1186/s12903-020-01306-0. DOI: https://doi.org/10.1186/s12903-020-01306-0

Venugopal A, Uma Maheswari TN. Expression of matrix metalloproteinase-9 in oral potentially malignant disorders: A systematic review. J Oral Maxillofac Pathol. 2016;20(3):474-479. doi: 10.4103/0973-029X.190951. DOI: https://doi.org/10.4103/0973-029X.190951

Laronha H, Caldeira J. Structure and Function of Human Matrix Metalloproteinases. Cells. 2020;9(5):1076. doi: 10.3390/cells9051076. DOI: https://doi.org/10.3390/cells9051076

Mughees M, Sengupta A, Khowal S, Wajid S. Mechanism of tumour microenvironment in the progression and development of oral cancer. Mol Biol Rep. 2021;48(2):1773-1786. doi: 10.1007/s11033-020-06054-6. DOI: https://doi.org/10.1007/s11033-020-06054-6

Walker C, Mojares E, Del Río Hernández A. Role of Extracellular Matrix in Development and Cancer Progression. Int J Mol Sci. 2018;19(10):3028. doi: 10.3390/ijms19103028. DOI: https://doi.org/10.3390/ijms19103028

Peisker A, Raschke GF, Fahmy MD, Guentsch A, Roshanghias K, Hennings J, 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. DOI: https://doi.org/10.4317/medoral.21626

Abbas SM, Dhahi MA. Relationship between human telomerase reverse transcriptase gene and some microRNAs expression levels in patients with bladder cancer. Al-Rafidain J Med Sci. 2024;7(1):215-220. doi: 10.54133/ajms.v7i1.1229. DOI: https://doi.org/10.54133/ajms.v7i1.1229

Abbas SM, Dhahi MA, Muhammad SH. Evaluation of gene expression level of miRNA-29c, miRNA-125, miRNA-141, miRNA-145 and miRNA-205 as predisposing factors for transitional cell carcinoma-bladder cancer in Iraqi patients. Iraqi J Sci. 2023;64(8):3799-3811. doi: 10.24996/ijs.2023.64.8.7. DOI: https://doi.org/10.24996/ijs.2023.64.8.7