Combination Assay for Tumor Markers in Saliva of Potentially Malignant Disorders and Oral Squamous Cell Carcinoma
Journal of Pharmaceutical Research International,
Potentially malignant disorders are “the risk of malignancy being present in a lesion or condition either at the time of initial diagnosis or at a future date” include mainly leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis. Biomarkers were of immense help in diagnosis in recent years but a very few molecular biomarkers have been reported in the literature which are not significantly accurate. The current study aims at quantifying the levels of Transforming growth factor (TGF- β), Platelet derived growth factors (PDGF) and receptor of advanced glycosylation end products (RAGE) in saliva of patients with potentially malignant disorders and oral squamous cell carcinoma. Unstimulated saliva of oral squamous cell carcinoma and potentially malignant disorder patients was collected and stored in sub zero temperature. Further biochemical analysis was performed with Raybio ELISA kits. One way ANOVA was performed. The mean concentration of RAGE, PDGF and TGF- β was increased in oral squamous cell carcinoma groups and potentially malignant disorders when compared to healthy controls.p-0.000 (p<0.05).These combined assays can be used as potential biomarkers for indicating the prognosis of the disease and can be used as a diagnostic tool for screening and early detection as these combined assays give more reliable and accurate diagnosis when compared to single biomarker assays.
- TGF- β
- potentially malignant disorders
- oral squamous cell carcinoma
How to Cite
Choi S, Myers JN. Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy [internet]. Journal of Dental Research. 2008;87:14-32.
Parkin DM, Maxwell Parkin D, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan [Internet]. 2000;94. International Journal of Cancer. 2001;153-6.
Kaur J, Srivastava A, Ralhan R. Overexpression of p53 protein in betel- and tobacco-related human oral dysplasia and squamous-cell carcinoma in India [Internet]. International Journal of Cancer. 1994;58:340–5.
Paterson IC, Eveson JW, Prime SS. Molecular changes in oral cancer may reflect aetiology and ethnic origin. Eur J Cancer B Oral Oncol. 1996;32(3):150–3.
Scully C, Bagan J. Oral squamous cell carcinoma overview [Internet]. Oral Oncology. 2009;45;301-8.
Sarode SC, Sarode GS, Tupkari JV. Oral potentially malignant disorders: A proposal for terminology and definition with review of literature. J Oral Maxillofac Pathol. 2014; 18(1):77–80.
Parakh MK, Ulaganambi S, Ashifa N, Premkumar R, Jain AL. Oral potentially malignant disorders: Clinical diagnosis and current screening aids: A narrative review. Eur J Cancer Prev. 2020;29(1):65–72.
Dror Luger, Lalage M. Wakefield inflammation and beyond: Complex roles for TGF- β in the tumor microenvironment [Internet]. The Inflammatory Milieu of Tumors: Cytokines and Chemokines that Affect Tumor Growth and Metastasis. 2012;123–54.
Meulmeester E, ten Dijke P. The dynamic roles of TGF-β in cancer [Internet]. The Journal of Pathology. 2011;223;206-19.
Demoulin J-B, Essaghir A. PDGF receptor signaling networks in normal and cancer cells. Cytokine Growth Factor Rev. 2014; 25(3):273–83.
Zhang M, Liu T, Xia B, Yang C, Hou S, Xie W, et al. Platelet-derived growth factor d is a prognostic biomarker and is associated with platinum resistance in epithelial ovarian cancer. Int J Gynecol Cancer. 2018;28(2):323–31.
Hermanson M, Funa K, Hartman M, Claesson-Welsh L, Heldin CH, Westermark B, et al. Platelet-derived growth factor and its receptors in human glioma tissue: Expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res. 1992;52(11):3213-9.
Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med. 2005;83(11):876-86.
Xie J, Méndez JD, Méndez-Valenzuela V, Aguilar-Hernández MM. Cellular signalling of the receptor for advanced glycation end products (RAGE). Cell Signal. 2013; 25(11):2185–97.
Ramasamy R, Yan SF, Schmidt AM. RAGE: therapeutic target and biomarker of the inflammatory response-the evidence mounts [Internet]. Journal of Leukocyte Biology. 2009;86:505-12.
Lee H, Park J-R, Kim WJ, Sundar IK, Rahman I, Park S-M, et al. Blockade of RAGE ameliorates elastase-induced emphysema development and progression via RAGE-DAMP signaling [Internet]. The FASEB Journal. 2017;31:2076–89.
Subramaniam N, Muthukrishnan A. Oral mucositis and microbial colonization in oral cancer patients undergoing radiotherapy and chemotherapy: A prospective analysis in a tertiary care dental hospital. J Investig Clin Dent. 2019;10(4):12454.
Vadivel JK, Govindarajan M, Somasundaram E, Muthukrishnan A. Mast cell expression in oral lichen planus: A systematic review. J Investig Clin Dent. 2019;10(4):12457.
Patil SR, Maragathavalli G, Ramesh DNSV, Vargheese S, Al-Zoubi IA, Alam MK. Assessment of maximum bite force in oral submucous fibrosis patients: A Preliminary Study. Pesqui Bras Odontopediatria Clin Integr. 2020;20:482.
Patil SR, Maragathavalli G, Araki K, Al-Zoubi IA, Sghaireen MG, Gudipaneni RK, et al. Three-rooted mandibular first molars in a Saudi Arabian Population: A CBCT Study. Pesqui Bras Odontopediatria Clin Integr. 2018;18(1):4133.
Patil SR, Yadav N, Al-Zoubi IA, Maragathavalli G, Sghaireen MG, Gudipaneni RK, et al. Comparative study of the efficacy of newer antioxitands lycopene and oxitard in the treatment of oral submucous fibrosis. Pesqui Bras Odontopediatria Clin Integr. 2018;18(1):1–7.
Jeng JH, Kuo ML, Hahn LJ, Kuo MYP. Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro [Internet]. Journal of Dental Research. 1994;73:1043–9.
Abelev GI, Perova SD, Khramkova NI, Postnikova ZA, Irlin IS. Production of embryonal α-globulin by transplantable mouse hepatomas [Internet]. Transplan-tation. 1963;1:174–80.
Zurawski VR, Knapp RC, Einhorn N, Kenemans P, Mortel R, Ohmi K, et al. An initial analysis of preoperative serum CA 125 levels in patients with early stage ovarian carcinoma [Internet]. Gynecologic Oncology. 1988;30:7–14.
Holmgren J, Lindholm L, Persson B, Lagergard T, Nilsson O, Svennerholm L, et al. Detection by monoclonal antibody of carbohydrate antigen CA 50 in serum of patients with carcinoma [Internet]. BMJ. 1984;288:1479-82.
Kew MC, Berger EL. The value of serum concentrations of tissue polypeptide antigen in the diagnosis of hepatocellular carcinoma [Internet]. Cancer. 1986;58: 127–30.
Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer P. Colorectal carcinoma antigens detected by hybridoma antibodies [Internet]. Somatic Cell Genetics. 1979;5:957–71.
Butler J. The Bronchial Circulation. CRC Press. 1992;832.
Richter GW. Comparison of Ferritins from Neoplastic and Non-Neoplastic Human Cells [Internet]. Nature. 1965;207:616–8.
Li J, Chen P, Mao C-M, Tang X-P, Zhu L-R. Evaluation of diagnostic value of four tumor markers in bronchoalveolar lavage fluid of peripheral lung cancer [Internet]. Asia-Pacific Journal of Clinical Oncology. 2014;10:141-8.
Paganuzzi M, Onetto M, Marroni P, Barone D, Conio M, Aste H, et al. CA 19-9 and CA 50 in benign and malignant pancreatic and biliary diseases. Cancer. 1988;61(10): 2100-8.
Kurokawa H, Tsuru S, Okada M, Nakamura T, Kajiyama M. Evaluation of tumor markers in patients with squamous cell carcinoma in the oral cavity [Internet]. International Journal of Oral and Maxillofacial Surgery. 1993;22:35–8.
Vinzenz K, Schönthal E, Zekert F, Wunderer S. Diagnosis of head and neck carcinomas by means of immunological tumour markers [Internet]. Journal of Cranio-Maxillofacial Surgery. 1987;15: 270–7.
Prasad G, McCullough M. Chemokines and Cytokines as Salivary Biomarkers for the Early Diagnosis of Oral Cancer [Internet]. International Journal of Dentistry. 2013;2013:1–7.
Piva MR, de Souza LB, Martins-Filho PRS, Nonaka CFW, de Santana Santos T, de Souza Andrade ES, et al. Role of inflammation in oral carcinogenesis (Part II): CD8, FOXP3, TNF-α, TGF-β and NF-κB expression [Internet]. Oncology Letters. 2013;5:1909–14.
Massagué J. TGFβ in Cancer [Internet]. Cell. 2008;134:215–30.
Polz-Dacewicz M, Strycharz-Dudziak M, Dworzański J, Stec A, Kocot J. Salivary and serum IL-10, TNF-α, TGF-β, VEGF levels in oropharyngeal squamous cell carcinoma and correlation with HPV and EBV infections. Infect Agent Cancer. 2016; 11:45.
Prime SS, Davies M, Pring M, Paterson IC. The role of TGF-beta in epithelial malignancy and its relevance to the pathogenesis of oral cancer (part II). Crit Rev Oral Biol Med. 2004;15(6):337–47.
Gonçalves AS, Mosconi C, Jaeger F, Wastowski IJ, Aguiar MCF, Silva TA, et al. Overexpression of immunomodulatory mediators in oral precancerous lesions. Hum Immunol. 2017;78(11-12):752–7.
Böhrnsen F, Godek F, Kiesel J, Kramer FJ, Brockmeyer P, Schliephake H. Influence of TGF-β1 on tumor transition in oral cancer cell and BMSC co-cultures. J Craniomaxillofac Surg. 2017;45(5):731-40.
Li H, Fredriksson L, Li X, Eriksson U. PDGF-D is a potent transforming and angiogenic growth factor. Oncogene. 2003; 22(10):1501-10.
Lin LH, Lin JS, Yang CC, Cheng HW, Chang KW, Liu CJ. Overexpression of Platelet-Derived Growth Factor and Its Receptor Are Correlated with Oral Tumorigenesis and Poor Prognosis in Oral Squamous Cell Carcinoma. Int J Mol Sci [Internet]. 2020;21(7).
Tsuzuki H, Sunaga H, Ito T, Narita N, Sugimoto C, Fujieda S. Reliability of platelet-derived endothelial cell growth factor as a prognostic factor for oral and oropharyngeal carcinomas. Arch Otolaryngol Head Neck Surg. 2005; 131(12):1071–8.
Kartha VK, Stawski L, Han R, Haines P, Gallagher G, Noonan V, et al. PDGFRβ Is a Novel Marker of Stromal Activation in Oral Squamous Cell Carcinomas. PLoS One. 2016;11(4):0154645.
Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, et al. RAGE Mediates a Novel Proinflammatory Axis [Internet]. Cell. 1999;97:889–901.
Hori O, Brett J, Slattery T, Cao R, Zhang J, Chen JX, et al. The Receptor for Advanced Glycation End Products (RAGE) Is a Cellular Binding Site for Amphoterin: Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system [Internet]. Journal of Biological Chemistry. 1995;270: 25752–61.
Vissing H, Aagaard L, Tommerup N, Boel E. Localization of the human gene for advanced glycosylation end product-specific receptor (AGER) to chromosome 6p21.3. Genomics. 1994;24(3):606-8.
Bhawal UK, Ozaki Y, Nishimura M, Sugiyama M, Sasahira T, Nomura Y, et al. Association of expression of receptor for advanced glycation end products and invasive activity of oral squamous cell carcinoma. Oncology. 2005;69(3):246–55.
Sasahira T, Kirita T, Bhawal UK, Ikeda M, Nagasawa A, Yamamoto K, et al. The expression of receptor for advanced glycation end products is associated with angiogenesis in human oral squamous cell carcinoma [Internet]. Virchows Archiv. 2007;450:287–95.
Taguchi A, Blood DC, del Toro G, Canet A, Lee DC, Qu W, et al. Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature. 2000; 405(6784):354–60.
Abstract View: 390 times
PDF Download: 217 times