САР1 AS A SERUM MARKER FOR EARLY DETECTION OF LARYNGEAL AND HYPOPHARYNGEAL CANCERS

Squamous cell carcinoma of head and neck (SCCHN) is often asymptomatic until it reaches the advanced stage. Currently, there are no available markers that can accurately predict the risk of progression of epithelial dysplasia to squamous cell carcinoma.

The purpose of the study was to evaluate the feasibility of using the level of adenylyl cyclase-associated protein 1 (CAP-1) in the blood serum to identify groups of increased risk of cancer in patients with chronic laryngeal and hypopharyngeal hyperplasia associated with epithelial dysplasia.

Material and methods. The blood serums from 45 patients with SCCHN (T1–4N0–3M0), 12 patients  with chronic inflammatory laryngeal and hypopharyngeal diseases and 15 heath subjects were examined. The blood analysis was performed using the CAP1 ELISA kit (Cusabio) on the Biochrom Anthos 2020 Microplate IEA Reader.

Results. The serum level of САР1 was higher by 75 % in patients with SCCHN (Т1N0M0) than in patients with chronic hyperplastic laryngitis. Moreover, differences in the serum level of САР1 were observed between healthy subjects and patients with chronic laryngeal hyperplasia. In SCCHN patients with regional metastases, CAP1 concentration in the blood serum was 2 times higher compared to that observed in SCCHN patients without regional metastases (p≤0.01).

Conclusion. The study results showed the feasibility of using the level of CAP1 for distinguishing patients with chronic hyperplastic laryngitis from those with laryngeal cancer, as well as for early detection of SCCHN and the development of new method for prediction of disease.

1. Choinzonov E.L., Belevich Yu.V., Chizhevskaya S.Yu., Goldberg V.E., Frolova I.G., Chernov V.I., Goldberg A.V. Modern methods of treatment of patients with cancer of the larynx and hypopharynx. Siberian Journal of Oncology. 2016; 15 (3): 91–96. doi: 10.21294/1814-4861-2016-15-3-91-96. [in Russian]

2. Choinzonov E.L., Kondakova I.V., Spirina L.V., Lebedev I.N., Goldberg V.E., Chizhevskaya S.Yu., Shishkin D.A., Urazova L.N., Kakurina G.V., Bychkov V.A., Khrichkova T.Yu., Melnikov A.A. Squamous cell carcinoma of the head and neck: Molecular basis of pathogenesis. Moscow, 2016; 224 p. [in Russian]

3. Cheremisina O.V., Choinzonov E.L., Pankova O.V., Men’shikov K.Yu. Chronic hyperplastic laryngitis as a criterion for defining groups at high risk group of laryngeal cancer. Russian Otorhinolaryngology. 2013; 2 (63): 84–89. [in Russian]

4. Sokolov V.V., Telegina L.V., Gladyshev A.A., Frank G.A., Zavalishyna L.E., Belous T.A. Modern methods of diagnosing obligate precancer and early laryngeal cancer. Head and neck. Journal of the All-Russian Public Organization Federation of Specialists in the Treatment of Head and Neck Diseases. 2013; 3: 44–48. [in Russian]

5. Trukhacheva N.G., Frolova I.G., Novikov V.A., Velichko S.A., Shtin V.I. Opportunity of ophthalmosonography in the evaluation of prevalence of sinoorbital tumors. Radiology – Practice. 2009; 2: 4–9. [in Russian]

6. Kakurina G.V., Kondakova I.V., Cheremisina O.V., Shishkin D.A., Choynzonov E.L. Adenylyl cyclase-associated protein 1 in the development of head and neck squamous cell carcinomas. Bull Exp Biol Med. 2015; 11: 486–651. [in Russian]

7. Lee S., Lee H.C., Kwon Y.W., Lee S.E., Cho Y., Kim J., Lee S., Kim J.Y., Lee J., Yang H.M., Mook-Jung I., Nam K.Y., Chung J., Lazar M.A., Kim H.S. Adenylyl Cyclase-Associated Protein 1 Is a Receptor for Human Resistin and Mediates Inflammatory Actions of Human Monocytes. Cell Metabolism. 2014; 19 (3): 484–497. doi: 10.1016/j.cmet.2014.01.013.

8. Spirina L.V., Kondakova I.V., Choynzonov E.L., Chigevskaya S.Y., Shishkin D.A., Kulbakin D.Y. Expression of vascular endothelial growth factor and transcription factors HIF-1, NF-KB expression in squamous cell carcinoma of head and neck; association with proteasome and calpain activities. J Cancer Res Clin Oncol. 2013; 13 (4): 625–633. doi: 10.1007/s00432-012-1366-0.

9. Yamazaki K., Takamura M., Masugi Y., Mori T., Du W., Hibi T., Hiraoka N., Ohta T., Ohki M., Hirohashi S., Sakamoto M. Adenylate cyclase associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. Lab Invest. 2009; 89 (4): 425–32. doi: 10.1038/labinvest.2009.5.

10. Poli G., Ceni E., Armignacco R., Ercolino T., Canu L., Baroni G., Nesi G., Galli A., Mannelli M., Luconi M. 2D-DIGE proteomic analysis identifies new potential therapeutic targets for adrenocortical carcinoma. Oncotarget. 2015; 6 (8): 5695–706.

11. Hua M., Yan S., Deng Y., Xi Q., Liu R., Yang S., Liu J., Tang C., Wang Y., Zhong J. CAP1 is overexpressed in human epithelial ovarian cancer and promotes cell proliferation. Int J Mol Med. 2015; 35 (4): 941–949. doi: 10.3892/ijmm.2015.2089.

12. Balabolkin M.I., Klebanova E.M. Hormones of adipose tissue and their role in the pathogenesis of diabetes II type. Lecatschiy vrach. 2010; 11: 27. [in Russian]

13. Li M., Yang X., Shi H., Ren H., Chen X., Zhang S., Zhu J., Zhang J. Downregulated Expression of the Cyclase-associated Protein 1 (CAP1) Reduces Migration in Esophageal Squamous Cell Carcinoma. Jpn J Clin Oncol. 2013; 43 (9): 856–864. doi: 10.1093/jjco/hyt093.

14. Zhang H., Ghai P., Wu H., Wang C., Field J., Zhou G.L. Mammalian adenylyl cyclase-associated protein 1 (CAP1) regulates cofilin function, the actin cytoskeleton, and cell adhesion. J Biol Chem. 2013; 288 (29): 20966–77. doi: 10.1074/jbc.M113.484535.

15. Liu X., Yao N., Qian J., Huang H. High expression and prognostic role of CAP1 and CtBP2 in breast carcinoma: associated with E-cadherin and cell proliferation. Med Oncol. 2014; 31 (3): 878. doi: 10.1007/s12032-014-0878-7.