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Predictive value of salivary microRNA-320a, vascular endothelial growth factor receptor 2, CRP and IL-6 in Oral lichen planus progression

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Abstract

Introduction

MicroRNA (miRNA) 320a and vascular endothelial growth factor receptor 2 (VEGFR-2) expression as the angiogenic biomarkers might be therapeutic targets in Oral lichen planus (OLP). IL-6 and C-reactive protein (CRP) could be prognostic in OLP, dysplastic OLP and Oral squamous cell carcinoma (OSCC). Therefore, their salivary detections as the noninvasive tools were aimed in this study.

Materials and methods

Histopathologic examinations were carried out to distinguish the patients with dysplastic OLP and OSCC. Salivary microRNA expression analysis was performed using RT-qPCR. IL-6 and CRP levels were also measured in saliva via ELISA method. VEGFR-2 expression in various sections was evaluated using immunohistochemistry.

Results

A significant decrease in salivary microRNA-320a in dysplastic OLP and OSCC but not in OLP without dysplasia was found. VEGFR-2 visualization confirmed the increasing angiogenic process in these cases. A significant increase in IL-6 level was detected in cases with OLP, dysplastic OLP and OSCC. CRP levels also showed a significant increase in dysplastic OLP and OSCC. A positive correlation between IL-6 and CRP levels was found.

Conclusion

Identification of the salivary microRNA-320a and hs-CRP might provide a convenient noninvasive predictive tool for dysplastic OLP, whereas IL-6 could be a diagnostic and therapeutic target in both OLP without dysplasia and dysplastic OLP cases.

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References

  • Ataie-Kachoie P, Pourgholami MH, Morris DL (2013) Inhibition of the IL-6 signaling pathway: a strategy to combat chronic inflammatory diseases and cancer. Cytokine Growth Factor Rev 24(2):163–173

    Article  CAS  PubMed  Google Scholar 

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brailo V, Vučićević-Boras V, Cekić-Arambašin A, Alajbeg I, Milenović A, Lukač J (2006) The significance of salivary interleukin 6 and tumour necrosis factor alpha in patients with oral leukoplakia. Oral Oncol 42(4):370–373

    Article  CAS  PubMed  Google Scholar 

  • Chainani-Wu Madden NE, Lozada-Nur F, Silverman S (2012) High-dose curcuminoids are efficacious in the reduction in symptoms and signs of oral lichen planus. J Am Acad Dermatol 66(5):752–760

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Malhotra PS, Thomas GR, Ondrey FG, Duffey DC, Smith CW, Enamorado I, Yeh NT, Kroog GS, Rudy S (1999) Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res 5(6):1369–1379

    CAS  PubMed  Google Scholar 

  • Chen CC et al (2010) Significance of interleukin-6 signaling in the resistance of pharyngeal cancer to irradiation and the epidermal growth factor receptor inhibitor. Int J Radiat Oncol 76(4):1214–1224

    Article  CAS  Google Scholar 

  • Chen MF, Lin PY, Wu CF, Chen WC, Wu CT (2013) IL-6 expression regulates tumourigenicity and correlates with prognosis in bladder cancer. PLoS One 8(4):e61901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duffy SA, Taylor JM, Terrell JE, Islam M, Li Y, Fowler KE, Tand Wolf G, Teknos TN (2008) Interleukin-6 predicts recurrence and survival among head and neck cancer patients. Cancer 113(4):750–757

    Article  PubMed  Google Scholar 

  • Fang HY, Huang XY, Chien HT, Chang GTC, Liao CT, Huang JJ, Wei FC, Wang HM, Chen IH, Kang CJ (2013) Refining the role of preoperative C-reactive protein by neutrophil/lymphocyte ratio in oral cavity squamous cell carcinoma. Laryngoscope 123(11):2690–2699

    Article  CAS  PubMed  Google Scholar 

  • Farazi TA, Spitzer JI, Morozov P, Tuschl T (2011) miRNAs in human cancer. J. Pathol 223(2):102–115

    Article  CAS  PubMed  Google Scholar 

  • Goda H, Okamoto M, Nakashiro KI, Tokuzen N, Hamakawa H (2015) 7PAnti-interleukin-6 receptor antibody suppressed oral squamous cell carcinoma by inhibiting tumour-stroma interaction. Ann Oncol 26(suppl 9):ix2

    Article  Google Scholar 

  • Gonzalez-Moles M, Scully C, Gil-Montoya J (2008) Oral lichen planus: controversies surrounding malignant transformation. Oral Dis 14(3):229–243

    Article  CAS  PubMed  Google Scholar 

  • Hashemy SI, Gharaei S, Vasigh S, Kargozar S, Alirezaei B, Jahed Keyhani F, Amirchaghmaghi M (2016) Oxidative stress factors and C-reactive protein in patients with oral lichen planus before and 2 weeks after treatment. J Oral Pathol Med 45(1):35–40

    Article  CAS  PubMed  Google Scholar 

  • Hu JY, Zhang J, Cui JL, Liang XY, Lu R, Du GF, Yand XuX, Zhou G (2013) Increasing CCL5/CCR5 on CD4+ T cells in peripheral blood of oral lichen planus. Cytokine 62(1):141–145

    Article  CAS  PubMed  Google Scholar 

  • Huang SF, Wei FC, Liao CT, Wang HM, Lin CY, Lo S, Huang JJ, Chen IH, Kang CJ, Chien HT (2012) Risk stratification in oral cavity squamous cell carcinoma by preoperative CRP and SCC antigen levels. Ann Surg Oncol 19(12):3856–3864

    Article  PubMed  Google Scholar 

  • Jinno T, Kawano S, Maruse Y, Matsubara R, Goto Y, Sakamoto T, Hashiguchi Y, Kaneko N, Tanaka H, Kitamura R (2015) Increased expression of interleukin-6 predicts poor response to chemoradiotherapy and unfavorable prognosis in oral squamous cell carcinoma. Oncol Rep 33(5):2161–2168

    CAS  PubMed  PubMed Central  Google Scholar 

  • John MAS, Li Y, Zhou X, Denny P, Ho CM, Montemagno C, Shi W, Qi F, Wu B, Sinha U (2004) Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 130(8):929–935

    Article  Google Scholar 

  • Juretic M, Cerovic R, Belusic-Gobic M, Prso IB, Kqiku L, Spalj S, Pezelj-Ribaric S (2013) Salivary levels of TNF-[alpha] and IL-6 in patients with oral premalignant and malignant lesions. Folia Biol 59(2):99

    CAS  Google Scholar 

  • Metgud R, Bajaj S (2016) Altered serum and salivary C-reactive protein levels in patients with oral premalignant lesions and oral squamous cell carcinoma. Biotech Histochem 91(2):96–101

    Article  CAS  PubMed  Google Scholar 

  • Min A, Zhu C, Peng S, Rajthala S, Costea DE, Sapkota D (2015) MicroRNAs as important players and biomarkers in oral carcinogenesis. BioMed Res Int 2015

  • Nakayama M, Tabuchi K, Hara A (2015) Clinical utility of the modified Glasgow prognostic score in patients with advanced head and neck cancer. Head Neck 37(12):1745–1749

    Article  PubMed  Google Scholar 

  • Navazesh M (1993) Methods for collecting saliva. Ann N Y Acad Sci 694(1):72–77

    Article  CAS  PubMed  Google Scholar 

  • Rhodus NL, Cheng B, Myers S, Miller L, Ho V, Ondrey F (2005) The feasibility of monitoring NF-κB associated cytokines: TNF-α, IL-1α, IL-6, and IL-8 in whole saliva for the malignant transformation of oral lichen planus. Mol Carcinog 44(2):77–82

    Article  CAS  PubMed  Google Scholar 

  • Shahidi M, Razavi SM, Hayat P (2016) Induction of endothelial cell proliferation and von Willebrand factor expression and secretion by leukemic plasma of patients with chronic lymphocytic leukemia before and after inhibition of NF-[kappa] B. Blood Coagul Fibrinolysis 27(6):711–716

    Article  CAS  PubMed  Google Scholar 

  • Tovaru S, Parlatescu I, Gheorghe C, Tovaru M, Costache M, Sardella M (2013) Oral lichen planus: a retrospective study of 633 patients from Bucharest, Romania. Med Oral Patol Oral Cir Bucal 18:e201–e206

    Article  PubMed  Google Scholar 

  • Tzeng HE, Tsai CH, Chang ZL, Su CM, Wang SW, Hwang WL, Tang CH (2013) Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma. Biochem Pharmacol 85(4):531–540

    Article  CAS  PubMed  Google Scholar 

  • Vucicević BV, Cikes N, Lukać J, Virag M, Cekić-Arambasin A (2005) Salivary and serum interleukin 6 and basic fibroblast growth factor levels in patients with oral squamous cell carcinoma. Minerva Stomatol 54(10):569–573

    Google Scholar 

  • Warnakulasuriya S, Johnson N, Van der Waal I (2007) Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 36(10):575–580

    Article  CAS  PubMed  Google Scholar 

  • Wu YY, Chen YL, Jao YC, Hsieh IS, Chang KC, Hong TM (2014) miR-320 regulates tumour angiogenesis driven by vascular endothelial cells in oral cancer by silencing neuropilin 1. Angiogenesis 17(1):247–260

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, Liu CG, Giannakakis A, Alexiou P, Hasegawa K (2008) Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci USA 105(19):7004–7009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We would like to thank the Iran University of Medical Science for supporting this project.

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Correspondence to Minoo Shahidi.

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There is no conflict of interests that could be perceived as influencing the objective of this research.

Ethical considerations

The work was approved by the Medical Ethics Committee of Iran University of Medical Sciences (IR.IUMS.REC.1395.25316) and written informed consent was obtained from all cases.

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Shahidi, M., Jafari, S., Barati, M. et al. Predictive value of salivary microRNA-320a, vascular endothelial growth factor receptor 2, CRP and IL-6 in Oral lichen planus progression. Inflammopharmacol 25, 577–583 (2017). https://doi.org/10.1007/s10787-017-0352-1

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