Emerging Role of Decoy Receptor-2 As a Cancer Risk Predictor in Oral Potentially Malignant Disorders

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Sep 28

PMID 37762685

Authors

Lucas de Villalain

Saul Alvarez-Teijeiro

Tania Rodriguez-Santamarta

Alvaro Fernandez Del Valle

Eva Allonca

Juan P Rodrigo

Juan Carlos de Vicente

Juana M Garcia-Pedrero

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to evaluate the expression of the senescence markers, Decoy Receptor 2 (DcR2) and Differentiated Embryo-Chondrocyte expressed gen 1 (DEC1), in oral potentially malignant disorders (OPMDs) to ascertain their possible association with oral cancer risk. The immunohistochemical analysis of DcR2 and DEC1 expression (along with p16 and Ki67 expression) was carried out in 60 patients with clinically diagnosed oral leukoplakia. Fifteen cases (25%) subsequently developed an invasive carcinoma. Correlations between protein marker expression, histological grade and oral cancer risk were assessed. DcR2, DEC1 and Ki67 protein expressions were found to correlate significantly with increased oral cancer risk, and also with an increased grade of dysplasia. Multivariate analysis demonstrated that DcR2 and Ki67 expression are independent predictors of oral cancer development. Our results evidence for the first time the potential of DcR2 as an early biomarker to assess oral cancer risk in patients with oral leukoplakia (HR = 59.7, = 0.015), showing a superior predictive value to histology (HR = 4.225, = 0.08). These findings reveal that the increased expression of DcR2 and DEC1 occurred frequently in OPMDs. In addition, DcR2 expression emerges as a powerful biomarker for oral cancer risk assessment in patients with oral leukoplakia.

References

Hu X, Wang W, Hu Y, Chen W, Wang C, Yang L . Overexpression of DEC1 in the epithelium of OSF promotes mesenchymal transition via activating FAK/Akt signal axis. J Oral Pathol Med. 2022; 51(9):780-790. DOI: 10.1111/jop.13350. View

de Vicente J, Rodrigo J, Rodriguez-Santamarta T, Lequerica-Fernandez P, Allonca E, Garcia-Pedrero J . Podoplanin expression in oral leukoplakia: tumorigenic role. Oral Oncol. 2013; 49(6):598-603. DOI: 10.1016/j.oraloncology.2013.02.008. View

Bascones-Martinez A, Lopez-Duran M, Cano-Sanchez J, Sanchez-Verde L, Diez-Rodriguez A, Aguirre-Echebarria P . Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans. Oncol Lett. 2012; 3(6):1319-1325. PMC: 3392562. DOI: 10.3892/ol.2012.649. View

Torres-Rendon A, Roy S, Craig G, Speight P . Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas. Br J Cancer. 2009; 100(7):1128-34. PMC: 2669983. DOI: 10.1038/sj.bjc.6604967. View

Sancilio S, Di Giacomo V, Quaglietta A, Iacone A, Angelucci D, Tatasciore U . TRAIL promotes a pro-survival signal in erythropoietin-deprived human erythroblasts through the activation of an NF-kB/IkBalpha pathway. J Biol Regul Homeost Agents. 2011; 25(3):375-86. View

Micheau O, Shirley S, Dufour F . Death receptors as targets in cancer. Br J Pharmacol. 2013; 169(8):1723-44. PMC: 3753832. DOI: 10.1111/bph.12238. View

Collado M, Serrano M . The power and the promise of oncogene-induced senescence markers. Nat Rev Cancer. 2006; 6(6):472-6. DOI: 10.1038/nrc1884. View

Nasser W, Flechtenmacher C, Holzinger D, Hofele C, Bosch F . Aberrant expression of p53, p16INK4a and Ki-67 as basic biomarker for malignant progression of oral leukoplakias. J Oral Pathol Med. 2011; 40(8):629-35. DOI: 10.1111/j.1600-0714.2011.01026.x. View

Kuilman T, Michaloglou C, Mooi W, Peeper D . The essence of senescence. Genes Dev. 2010; 24(22):2463-79. PMC: 2975923. DOI: 10.1101/gad.1971610. View

10.

Parrinello S, Coppe J, Krtolica A, Campisi J . Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J Cell Sci. 2005; 118(Pt 3):485-96. PMC: 4939801. DOI: 10.1242/jcs.01635. View

11.

Vigneswaran N, Baucum D, Wu J, Lou Y, Bouquot J, Muller S . Repression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not its receptors during oral cancer progression. BMC Cancer. 2007; 7:108. PMC: 1924860. DOI: 10.1186/1471-2407-7-108. View

12.

Campo-Trapero J, Cano-Sanchez J, Palacios-Sanchez B, Llamas-Martinez S, Lo Muzio L, Bascones-Martinez A . Cellular senescence in oral cancer and precancer and treatment implications: a review. Acta Oncol. 2008; 47(8):1464-74. DOI: 10.1080/02841860802183612. View

13.

Coppe J, Desprez P, Krtolica A, Campisi J . The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99-118. PMC: 4166495. DOI: 10.1146/annurev-pathol-121808-102144. View

14.

Anees M, Horak P, El-Gazzar A, Susani M, Heinze G, Perco P . Recurrence-free survival in prostate cancer is related to increased stromal TRAIL expression. Cancer. 2011; 117(6):1172-82. DOI: 10.1002/cncr.25504. View

15.

Mahalingam D, Szegezdi E, Keane M, de Jong S, Samali A . TRAIL receptor signalling and modulation: Are we on the right TRAIL?. Cancer Treat Rev. 2009; 35(3):280-8. DOI: 10.1016/j.ctrv.2008.11.006. View

16.

Qian Y, Jung Y, Chen X . Differentiated embryo-chondrocyte expressed gene 1 regulates p53-dependent cell survival versus cell death through macrophage inhibitory cytokine-1. Proc Natl Acad Sci U S A. 2012; 109(28):11300-5. PMC: 3396538. DOI: 10.1073/pnas.1203185109. View

17.

Angiero F, Berenzi A, Benetti A, Rossi E, Del Sordo R, Sidoni A . Expression of p16, p53 and Ki-67 proteins in the progression of epithelial dysplasia of the oral cavity. Anticancer Res. 2008; 28(5A):2535-9. View

18.

Walczak H . Death receptor-ligand systems in cancer, cell death, and inflammation. Cold Spring Harb Perspect Biol. 2013; 5(5):a008698. PMC: 3632055. DOI: 10.1101/cshperspect.a008698. View

19.

van der Waal I . Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol. 2008; 45(4-5):317-23. DOI: 10.1016/j.oraloncology.2008.05.016. View

20.

Kannan S, Chandran G, Pillai K, Mathew B, Sujathan K, Nalinakumary K . Expression of p53 in leukoplakia and squamous cell carcinoma of the oral mucosa: correlation with expression of Ki67. Clin Mol Pathol. 1996; 49(3):M170-5. PMC: 408045. DOI: 10.1136/mp.49.3.m170. View