Preview

Bulletin of Siberian Medicine

Advanced search

Molecular features of head and neck squamous cell carcinoma

https://doi.org/10.20538/1682-0363-2018-3-61-69

Abstract

Relevance. To identify new markers of early diagnosis and prognosis of head and neck squamous cell carcinoma (HNSCC) it is necessary to study the molecular features of this disease.

Purpose. The aim of the study was to analyze blood serum protein spectrum in patients with HNSCC and in healthy volunteers using the methods of mass spectrometry and to evaluate the selected serum protein markers as candidates for early detection of HNSCC.

Materials and Methods: The blood serum of HNSCC patients before therapy with metastases, without metastases and healthy volunteers was studied by proteomic methods. Validation of the results of proteomic analysis was carried out by ELISA in serum of 52 patients with HNSCC (T1-4N0-3M0), 10 patients with chronic hyperplastic laryngitis, dysplasia DII-DIII and 10 healthy volunteers. The statistical analysis was carried out using Statistica 6.0. Software package.

Results. Blood serum proteome of HNSCC patients with metastases, without metastases and healthy volunteers are different and contain proteins of different classes. Adenylyl cyclase-associated protein 1 (CAP1) and protein phosphatase 1B (PPM1B) were selected to validate the obtained results. It was shown that the serum level of CAP1 and PPM1B differed in control and dysplasia groups and dysplasia and cancer groups (p ≤ 0,05). In patients with HNSCC (T1N0M0) the serum CAP1 and PPM1B levels were higher than in patients with dysplasia and healthy individuals (p ≤ 0,05). It was noted the positive correlation of the CAP1 level in the serum with the presence of metastases and the PPM1B level.

Conclusion. Candidates for serum markers of HNSCC prognosis were identified. The difference in serum levels of CAP1 and PPM1B depending on the prevalence of primary tumors and the difference in serum level of CAP1 depending on the presence of regional metastases was shown. Determination of CAP1 level in the serum can be useful for early diagnosis and prognosis of HNSCC.

About the Authors

G. V. Kakurina
Cancer Research Institute, Tomsk National Research Medical Center (TNRМС) of Russian Academy of Science (RAS)
Russian Federation

Kakurina Gelena V. - PhD, Senior Researcher, Laboratory of Tumor Biochemistry.

5, Kooperativny Str., Tomsk, 634050



E. S. Kolegova
Cancer Research Institute, Tomsk National Research Medical Center (TNRМС) of Russian Academy of Science (RAS); Siberian State Medical University (SSMU)
Russian Federation

Kolegova Elena S. - Junior Researcher, Laboratory of Tumor Biochemistry, Cancer Research Institute, TNRMC RAS.

5, Kooperativny Str., Tomsk, 634050; 2, Moscow Trakt, Tomsk, 634050



О. V. Cheremisina
Cancer Research Institute, Tomsk National Research Medical Center (TNRМС) of Russian Academy of Science (RAS)
Russian Federation

Cheremisina Оlga V. - DM, Head of the Endoscopy Department.

5, Kooperativny Str., Tomsk, 634050



Е. L. Choinzonov
Cancer Research Institute, Tomsk National Research Medical Center (TNRМС) of Russian Academy of Science (RAS); Siberian State Medical University (SSMU)
Russian Federation

Choinzonov Еvgeny L. - DM, Professor, Academician of RAS, Director of TNRMC, Cancer Research Institute, TNRMC RAS; SSMU.

5, Kooperativny Str., Tomsk, 634050; 2, Moscow Trakt, Tomsk, 634050



References

1. Head and neck squamous cell carcinoma: Molecular basis of pathogenesis. Choynzonov E.L., Kondakova I.V., Spirina L.V., Lebedev I.N., Gol’dberg V.E., Chizhevskaya S.Yu., Shishkin D.A., Urazova L.N., Kakurina G.V., Bychkov V.A., Khrichkova T.Yu., Mel’nikov A.A. M.: Nauka Publ., 2016: 224 (in Russ.).

2. Kolegova E.S., Kondakova I.V., Zav’yalov A.A. Small heat shock proteins and the ubiquitin-proteasome system in malignant tumors. Voprosy onkologii – Problems of Oncology. 2016; 3: 401–405 (in Russ.)

3. Kakurina G.V., Kondakova I.V., Choinzonov E.L. Prognosing head and neck squamous cell carcinoma metastases. Voprosy onkologii – Problems of Oncology. 2012; 58 (1): 26–32 (in Russ.).

4. Shashova E.E., Astakhova T.M., Plekhanova A.S., Bogomyagkova Y.V., Lyupina Y.V., Sumedi I.R., Slonimskaya E.M., Erokhov P.A., Abramova E.B., Rodoman G.V., Kuznetsov N.A., Kondakova I.V., Sharova N.P., Choinzonov E.L. Changes in proteasome chymotrypsin-like activity during the development of human mammary and thyroid carcinomas. Byulleten’ eksperimental’noy biologii i meditsiny – Bulletin of Experimental Biology and Medicine. 2013; 156 (2): 242–244 (in Russ.).

5. Kondakova I.V., Zagrebelnaya G.V., Choinzonov E.Ts. Impact of NO-generating compounds on tumoritoxic effect of doxorubicin. Byulleten’ eksperimental’noy biologii i meditsiny – Bulletin of Experimental Biology and Medicine. 2004; 137 (6): 585– 587 (in Russ.).

6. Krishnan A.R., Zheng H., Kwok J.G., Qu Y., Zou A.E., Korrapati A., Li P.X., Califano J.A., Hovell M.F., WangRodriguez J., Ongkeko W.M. A comprehensive study of smoking-specific microRNA alterations in head and neck squamous cell carcinoma. Oral. Oncology. 2017; 72: 56–64.

7. Bochkareva N.V., Kondakova I.V., Kolomiets L.A. The role of actin binding proteins in normal and tumor cell motility. Molekulyarnaya meditsina. 2011; 6: 14–18 (in Russ.).

8. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248–254.

9. Rosenfeld J., Capdevielle J., Guillemot J.C., Ferrara P. In-gel digestion of proteins for internal sequence analysis after oneor two-dimensional gel electrophoresis. Anal. Biochem. 1992; 203 (1): 173–179.

10. Sun W., Yu Y., Dotti G., Shen T., Tan X., Savoldo B., Pass A.K., Chu M., Zhang D., Lu X., Fu S., Lin X., Yang J. PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha induced IKKbeta NF kappaB activation. Cell Signal. 2009; 2–1 (1): 95–102.

11. Takeuchi T., Kobayashi T., Tamura S., Yokosawa H. Negative regulation of protein phosphatase 2Cbeta by ISG15 conjugation. FEBS Lett. 2006; 580 (18): 4521– 4526.

12. Wang H., Chen Y., Han J., Meng Q., Xi Q., Wu G., Zhang B. DCAF4L2 promotes colorectal cancer invasion and metastasis via mediating degradation of NFκb negative regulator PPM1B. Am. J. Transl. Res. 2016; 8 (2): 405–418.

13. Yang J., Yuan D., Li J., Zheng S., Wang B. MiR-186 downregulates protein phosphatase PPM1B in bladder cancer and mediates G1-S phase transition. Tumour Biol. 2016; 37 (4): 4331–4341.

14. Zuo S., Xue Y., Tang S., Yao J., Du R., Yang P., Chen X. 14-3-3 epsilon dynamically interacts with key components of mitogen-activated protein kinase signal module for selective modulation of the TNF-alpha-induced time course-dependent NF-kappaB activity. J. Proteome Res. 2010; 9 (7): 3465–3478. DOI: 10.1021/pr9011377.

15. Chen W., Wu J., Li L., Zhang Z., Ren J., Liang Y., Chen F., Yang C., Zhou Z., Su S.S., Zheng X., Zhang Z., Zhong C.Q., Wan H., Xiao M., Lin X., Feng X.H., Han J. Ppm1b negatively regulates necroptosis through dephosphorylating Rip3. Nat. Cell Biol. 2015; 17 (4): 434–444. DOI: 10.1038/ncb3120.

16. Bertling E., Hotulainen P., Mattila P.K., Matilainen T., Salminen M., Lappalainen P. Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells. Molecular Biology of the Cell. 2004; 15 (5): 2324–2334.

17. 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.

18. 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.

19. 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.

20. 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): 425–432.

21. 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.

22. Tan M., Song X., Zhang G., Peng A., Li X., Li M., Liu Y., Wang C. Overexpression of adenylate cyclase-associated protein 1 is associated with metastasis of lung cancer. Oncol. Rep. 2013; Oct.; 30 (4): 1639–1644. DOI: 10.3892/OR.2013.2607.


Review

For citations:


Kakurina G.V., Kolegova E.S., Cheremisina О.V., Choinzonov Е.L. Molecular features of head and neck squamous cell carcinoma. Bulletin of Siberian Medicine. 2018;17(3):61-69. (In Russ.) https://doi.org/10.20538/1682-0363-2018-3-61-69

Views: 1024


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-0363 (Print)
ISSN 1819-3684 (Online)