• О. Kravets National Cancer Institute of Ministry of Health of Ukraine, Kyiv 03022, Ukraine
  • O. Burtyn National Cancer Institute of Ministry of Health of Ukraine, Kyiv 03022, Ukraine
  • T. Borikun RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NASU, Kyiv 03022, Ukraine
  • O. Rossylna Clinic for Personalized Diagnostics and Therapy Design “Oncotheranostics”, Kyiv 03022, Ukraine



oral squamous cell carcinoma miRNA, CDKN2A, p16INK4a prognosis


Background. Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Disco- vering novel prognostic markers for OSCC can improve treatment outcomes by allowing for more effective therapy strategies. Aim. To identify the prognostic value of CDKN2A (p16INK4a) and miRNAs involved in its regulation as markers of OSCC. Materials and Methods. The work is based on the results of the examination and treatment of 70 patients with stage II—IV OSCC. miR-10b, -155, and CDKN2A mRNA expression in tumor samples was ana- lyzed by real-time reverse transcription polymerase chain reaction. The expression of p16INK4a and Ki-67 proteins was determined immunohistochemically. Results. No association of CDKN2A mRNA and p16INK4a protein with Ki-67 expression in tumor tissue and clinical pathological parameters of OSCC patients was found. Most of the p16INK4a-positive cases were characterized by a high Ki-67 expression. We found a strong correlation of the studied miRNAs expression levels with lymph node metastasis (r = 0.56 for miR-10b and r = 0.59 for miR-155). Also, there was no difference in miR-10b and -155 expression between p16INK4a+ and p16INK4a– samples. The association of both miRNAs with lymph node metastases was not affected by p16INK4a status. Conclusions. The results indicate the relationship between miR-10b and -155 and the presence of lymph node metastases in OSCC patients, so these miRNAs can be considered as prognostic markers of the disease.


Hertel M, Hagedorn L, Schmidt-Westhausen AM, et al. Comparison of five-year survival rates among patients with oral squamous cell carcinoma with and without association with syphilis: a retrospective case-control study. BMC Cancer. 2022;22(1):1-7. doi: 10.1186/s12885-022-09583-4

Fedorenko ZP, Michailovich Yu, Goulak LO, et al. Cancer in Ukraine 2019-2020: incidence, mortality, prevalence and other relevant statistics. Bull Nat Cancer Reg Ukraine 2022:22. Available at

Bereznyuk DV, Kovtunenko OV, Tymchuk SM. Prognostic significance of the expression of matrix metallopro- teinases 1 and 9 in tumors in patients with squamous cell cancer of the oral part of the pharynx. J Ear, Nose Throat Dis. 2016;1: 20-27 (in Ukrainian).

Kravets ОV, Burtyn OV, Borikun TV, et al. Significance of expression of tumor-associated microrna-21 and- 375 for predicting the course of cancer of oral cavity. Exp Oncol. 2021;43(1):36-40. doi: 10.32471/exp-oncolo- gy.2312-8852.vol-43-no-1.15884

Padhi SS, Roy S, Kar M, et al. Role of CDKN2A/p16 expression in the prognostication of oral squamous cell car- cinoma. Oral Oncol 2017;73:27-35. doi: 10.1016/j.oraloncology.2017.07.030

Lu YC, Chen YJ, Wang HM, et al. Oncogenic function and early detection potential of miRNA-10b in oral cancer as identified by microRNA profiling. Cancer Prev Res (Phila). 2012;5(4):665-674. doi: 10.1158/1940-6207.CAPR- 11-0358

Wu M, Duan Q, Liu X, Zhang P, et al. MiR-155-5p promotes oral cancer progression by targeting chromatin remodeling gene ARID2. Biomed Pharmacother. 2020;122:109696. doi: 10.1016/j.biopha.2019.109696

Zadvornyi TV, Lukianova NY, Borikun TV, et al. NANOG as prognostic factor of prostate cancer course. Exp Oncol. 2020;42(2):94-100. doi: 10.32471/exp-oncology.2312-8852.vol-42-no-2.14673

Smitha T, Mohan CV, Hemavathy S. Prevalence of human papillomavirus16 DNA and p16INK4a protein in oral squamous cell carcinoma: A systematic review and meta-analysis. J Oral Maxillofac Pathol. 2017;21(1):76. doi: 10.4103/jomfp.JOMFP_248_16

Omer SM, Rashid PA. Immunoexpression of P16 and Ki 67 in oral squamous cell carcinoma: Association with clinicopathological parameters. Erbil Dent J. 2020;3(2):136-144. doi: 10.15218/edj.2020.19

Prigge ES, Toth C, Dyckhoff G, et al. p16INK4a/Ki-67 co-expression specifically identifies transformed cells in the head and neck region. Int J Cancer. 2015;136(7):1589-1599. doi: 10.1002/ijc.29130

Gołąbek K, Rączka G, Gaździcka J, et al. Expression profiles of CDKN2A, MDM2, E2F2 and LTF genes in oral squamous cell carcinoma. Biomed. 2022;10(12):3011. doi: 10.3390/biomedicines10123011

Zhang J, Yang J, Zhang X, et al. MicroRNA-10b expression in breast cancer and its clinical association. PLoS One. 2018;13(2):e0192509. doi: 10.1371/journal.pone.0192509

Severino P, Brüggemann H, Andreghetto FM, et al. MicroRNA expression profile in head and neck cancer: HOX- cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation. BMC Can­ cer. 2013;13:1-15. doi: 10.1186/1471-2407-13-533

Li S, Gao L, Liu J, et al. The microRNA-10b-Bim axis promotes cancer progression through activating autophagy in oral squamous cell carcinoma. Cell Death Discov. 2022;8(1):373. doi: 10.1038/s41420-022-01168-1

Manikandan M, Deva Magendhra Rao AK, Rajkumar KS, et al. Altered levels of miR-21, miR-125b-2*, miR-138, miR-155, miR-184, and miR-205 in oral squamous cell carcinoma and association with clinicopathological char- acteristics. J Oral Pathol Med. 2014;44(10):792-800. doi: 10.1111/jop.12300

Ni YH, Huang XF, Wang ZY, et al. Upregulation of a potential prognostic biomarker, miR-155, enhances cell pro- liferation in patients with oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117(2): 227-233. doi: 10.1016/j.oooo.2013.10.017

Dioguardi M, Spirito F, Sovereto D, et al. Biological prognostic value of miR-155 for survival outcome in head and neck squamous cell carcinomas: systematic review, meta-analysis and trial sequential analysis. Biol. 2022;11(5):651. doi: 10.1038/bjc.2011.29

Lajer CB, Nielsen FC, Friis-Hansen L, et al. Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study. Brit J Cancer. 2011;104(5):830-840. doi:

Lee SH, Lee CR, Rigas NK, et al. Human papillomavirus 16 (HPV16) enhances tumor growth and cancer stem- ness of HPV-negative oral/oropharyngeal squamous cell carcinoma cells via miR-181 regulation. Papillomavirus Res. 2015;1:116-125. doi: 10.1016/j.pvr.2015.08.001

Avram EG, Moatar IA, Miok V, et al. Gene network analysis of the transcriptome impact of methylated microR- NAs on oral squamous cell carcinoma Adv Clin Exp Med. 2022;31(11):1231-1242. doi: 10.17219/acem/151911




How to Cite

Kravets О., Burtyn, O., Borikun, T., & Rossylna, O. (2023). THE STUDY OF PROGNOSTIC VALUE OF microRNAs (miR-10b AND -155) AND CDKN2A/P16INK4A IN ORAL SQUAMOUS CELL CARCINOMA. Experimental Oncology, 45(2), 187–194.



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