Serum Concentration of MMP-9 As a Predictive Biomarker for the Progression of Oral Cancer

Overview

Journal J Maxillofac Oral Surg

Date 2024 Oct 8

PMID 39376770

Authors

Jyoti Saini

Jaimanti Bakshi

Naresh K Panda

Maryada Sharma

Ashok K Yadav

Kajal Kamboj

Atul Kumar Goyal

Affiliations

Soon will be listed here.

Abstract

Background: Oral cancer is the most prominent cancer subtype among all head and neck cancers, the incidence and prevalence of which has been consistently increasing in past years around the globe. At advanced stages, oral cancer imparts significant mortality, morbidity, and mutilation among the patients, and therefore, diagnosis and treatment of the disease at early stages are considered the optimum strategy for the management of the disease. Since molecular changes appear earlier than physical symptoms, several molecular biomarkers are currently being investigated for their role in diagnosing and treating disease. MMP-9 belongs to the family of proteinases that are involved in cytoskeletal degradation, which is a crucial phase of cancer progression.

Objective: In the present study, we analyzed the serum concentration of MMP-9 in oral cancer patients and tried to establish MMP-9 as a predictive biomarker for the progression of oral cancer. We also correlated the clinical, sociodemographic and biochemical parameters with the serum concentration of MMP-9 in oral cancer patients.

Methods: Serum was extracted from the blood sample of 38 oral cancer patients and was analyzed for the concentration of MMP-9 using sandwiched ELISA. Predesigned proforma was used to capture the clinical, sociodemographic and biochemical parameters. Unpaired t-test was used to compare two means, one way ANOVA was used to compare more than two means and Pearson's correlation was used to correlate the variables.

Results: The mean concentration of MMP-9 in patients of oral cancer was 816.9 ± 236.1 ng/mL. The MMP-9 expression level was higher at advanced oral cancer stages than in the early stages. No significant difference in the MMP expression was found in terms of sociodemographic risk factor and tumor site. MMP-9 exhibit significant negative correlation with the HDL and significantly positive correlation with the PTI. Rest of the biochemical parameters does not exhibit significant correlation.

Conclusion: The present study suggests that serum concentration of MMP-9 can be a predictive biomarker for the progression of oral cancer, which needs to be validated by performing further longitudinal cross-sectional studies by taking ample sample size.

References

Shpitzer T, Bahar G, Feinmesser R, Nagler R . A comprehensive salivary analysis for oral cancer diagnosis. J Cancer Res Clin Oncol. 2007; 133(9):613-7. DOI: 10.1007/s00432-007-0207-z. View

Fan H, Li H, Chen D, Gao Z, Zheng J . Changes in the expression of MMP2, MMP9, and ColIV in stromal cells in oral squamous tongue cell carcinoma: relationships and prognostic implications. J Exp Clin Cancer Res. 2012; 31:90. PMC: 3490717. DOI: 10.1186/1756-9966-31-90. View

Impola U, Uitto V, Hietanen J, Hakkinen L, Zhang L, Larjava H . Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer. J Pathol. 2003; 202(1):14-22. DOI: 10.1002/path.1479. View

Ikebe T, Shinohara M, Takeuchi H, Beppu M, Kurahara S, Nakamura S . Gelatinolytic activity of matrix metalloproteinase in tumor tissues correlates with the invasiveness of oral cancer. Clin Exp Metastasis. 1999; 17(4):315-23. DOI: 10.1023/a:1006642428826. View

Halade G, Jin Y, Lindsey M . Matrix metalloproteinase (MMP)-9: a proximal biomarker for cardiac remodeling and a distal biomarker for inflammation. Pharmacol Ther. 2013; 139(1):32-40. PMC: 3660444. DOI: 10.1016/j.pharmthera.2013.03.009. View

Smriti K, Ray M, Chatterjee T, Shenoy R, Gadicherla S, Pentapati K . 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. PMC: 7294014. DOI: 10.31557/APJCP.2020.21.1.233. View

Riedel F, Gotte K, Schwalb J, Hormann K . Serum levels of matrix metalloproteinase-2 and -9 in patients with head and neck squamous cell carcinoma. Anticancer Res. 2000; 20(5A):3045-9. View

Goyal A, Bakshi J, Panda N, Kapoor R, Vir D, Kumar K . Stigmatic Impact of COVID-19 Pandemic on Head & Neck Cancers Survivors. Indian J Otolaryngol Head Neck Surg. 2021; 74(Suppl 2):2912-2916. PMC: 8061151. DOI: 10.1007/s12070-021-02545-5. View

O-Charoenrat P, Rhys-Evans P, Eccles S . Expression of matrix metalloproteinases and their inhibitors correlates with invasion and metastasis in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 2001; 127(7):813-20. View

10.

Kato K, Hara A, Kuno T, Kitaori N, Huilan Z, Mori H . Matrix metalloproteinases 2 and 9 in oral squamous cell carcinomas: manifestation and localization of their activity. J Cancer Res Clin Oncol. 2004; 131(6):340-6. DOI: 10.1007/s00432-004-0654-8. View

11.

de Vicente J, Fresno M, Villalain L, Vega J, Hernandez Vallejo G . Expression and clinical significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in oral squamous cell carcinoma. Oral Oncol. 2005; 41(3):283-93. DOI: 10.1016/j.oraloncology.2004.08.013. View

12.

Lin C, Tseng S, Yang S, Ko C, Lin C, Wei L . Role of lipocalin 2 and its complex with matrix metalloproteinase-9 in oral cancer. Oral Dis. 2012; 18(8):734-40. DOI: 10.1111/j.1601-0825.2012.01938.x. View

13.

Lee B, Kim M, Jang H, Lee H, Ahn K, Lee J . A high concentration of MMP-2/gelatinase A and MMP-9/gelatinase B reduce NK cell-mediated cytotoxicity against an oral squamous cell carcinoma cell line. In Vivo. 2008; 22(5):593-7. View

14.

Shpitzer T, Hamzany Y, Bahar G, Feinmesser R, Savulescu D, Borovoi I . Salivary analysis of oral cancer biomarkers. Br J Cancer. 2009; 101(7):1194-8. PMC: 2768098. DOI: 10.1038/sj.bjc.6605290. View

15.

Lotfi A, Mohammadi G, Tavassoli A, Mousaviagdas M, Chavoshi H, Saniee L . Serum levels of MMP9 and MMP2 in patients with oral squamous cell carcinoma. Asian Pac J Cancer Prev. 2015; 16(4):1327-30. DOI: 10.7314/apjcp.2015.16.4.1327. View

16.

Katayama A, Bandoh N, Kishibe K, Takahara M, Ogino T, Nonaka S . Expressions of matrix metalloproteinases in early-stage oral squamous cell carcinoma as predictive indicators for tumor metastases and prognosis. Clin Cancer Res. 2004; 10(2):634-40. DOI: 10.1158/1078-0432.ccr-0864-02. View

17.

Zhou C, Gao Y, Johnson N, Gao J . Immunoexpression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the metastasis of squamous cell carcinoma of the human tongue. Aust Dent J. 2010; 55(4):385-9. DOI: 10.1111/j.1834-7819.2010.01258.x. View

18.

Kurahara S, Shinohara M, Ikebe T, Nakamura S, Beppu M, Hiraki A . Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis. Head Neck. 1999; 21(7):627-38. DOI: 10.1002/(sici)1097-0347(199910)21:7<627::aid-hed7>3.0.co;2-2. View

19.

Stanciu A, Zamfir-Chiru-Anton A, Stanciu M, Pantea-Stoian A, Nitipir C, Gheorghe D . Serum melatonin is inversely associated with matrix metalloproteinase-9 in oral squamous cell carcinoma. Oncol Lett. 2020; 19(4):3011-3020. PMC: 7068641. DOI: 10.3892/ol.2020.11392. View

20.

Cavusoglu E, Ruwende C, Chopra V, Yanamadala S, Eng C, Clark L . Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction. Am Heart J. 2006; 151(5):1101.e1-8. DOI: 10.1016/j.ahj.2006.02.029. View