Predicting the risk of cervical intraepithelial neoplasia associated with HPV infection malignisation using the combination of proteomics and transcriptomics


Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Acesso é pago ou somente para assinantes

Resumo

Objective. Study of the proteomic composition of cervicovaginal fluid to determine the risk of cervical neoplasia malignancy in reproductive age patients with HPV infection. Subjects and methods. The clinical examination, molecular biology methods, cytology, extended colposcopy, PCR, proteomics research of cervicovaginal fluid. Results. 4 group were formed including 30 women: 7 patients (23%) - NILM (I group - control), 23 (77%) - HPV-positive, divided into 3 groups: II group of 11 (49%) with ASCUS, III group - 7 (30%) with LSIL, IV group - 5 (21%) with HSIL. High-risk HPV was detected in 90.9% of cases in the group with ASCUS and 100% - in the group with LSIL and HSIL. The most common types of HPV are 16 (34.8%) 31 (17.4%) 52 58 56 (13%) 18 35 (8.7%), other types were at least 5%. 69% of patients had a viral load of 5.2log (on average - 5.6log) with no significant differences between groups. Normal normal colposcopic picture was in 7 (23%) patients, abnormal - 23 (87%). Significant separation of the control samples with NILM and groups with ASCUS, LSIL, HSIL was revealed by semi-quantitative analysis of proteomic composition of CVF. The concentration of heat shock proteins S100-A9, S100-P, S100-A11, HSPA8, acetyl- CoA-binding protein, Annexin A1 and A2 in the group with neoplasia was an order of magnitude higher compared to the control group. Multivariate analysis of patients’ proteome and transcriptome data was performed by PLS method. A significant clusterisation of the group with a low risk of development/progression of cervical dysplasia and high-risk group was achieved. CVF proteins which made a major contribution to this separation were associated with oncogenic processes, among which a special place belongs to malignant transformation of lung epithelium, esophagus, rectum, cervix and other types of HPV-associated cancers. Conclusion. CVF proteins which made an important contribution to the differentiation in the groups with normal cervical epithelium and groups with cervical neoplasia of varying severity were identified.

Texto integral

Acesso é fechado

Sobre autores

Nataliia Starodubtseva

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_starodubtseva@oparina4.ru
PhD, Head of Laboratory of Proteomics of Human Reproduction

Niso Nazarova

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: grab2@yandex.ru
MD, PhD, Senior Researcher

Maka Zardiashvili

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: z-m-d@mail.ru
PhD student

Olga Bourmenskaya

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: o_bourmenskaya@oparina4.ru
MD, Molecular-genetic Laboratory Researcher

Anna Bugrova

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a_bugrova@oparina4.ru
PhD, Senior Researcher of Proteomics of Human Reproduction

Vitaliy Chagovets

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: vvchagovets@gmail.com
PhD, Senior Researcher of Proteomics of Human Reproduction

Aleksey Kononikhin

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: konoleha@yandex.ru
PhD, Researcher of Proteomics of Human Reproduction

Dmitriy Trofimov

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: d.trofimov@dna-tech.ru
MD, PhD, Molecular-genetic Laboratory Chief

Vladimir Frankevich

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_frankevich@oparina4.ru
PhD, Head of Department of Systems Biology in Reproduction

Gennadiy Sukhikh

Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru
Academician of RAMS, MD, PhD, Professor, Director

Bibliografia

  1. Zur Hausen H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J. Natl. Cancer Inst. 2000; 92(9): 690-8.
  2. http : //www. cdc. gov/hpv
  3. Good D.M., Thongboonkerd V., Novak J., Bascands J.L., Schanstra J.P., Coon J.J. et al. Body fluid proteomics for biomarker discovery: lessons from the past hold the key to success in the future. J. Proteome Res. 2007; 6(12): 4549-55.
  4. Van Raemdonck G.A., Tjalma W.A., Coen E.P., Depuydt C.E., Van Ostade X.W.M. Identification of protein biomarkers for cervical cancer using human cervicovaginal fluid. PLoS One. 2014; 9(9): e106488.
  5. Zegels G., Van Raemdonck G.A., Tjalma W.A., Van Ostade X.W. Use of cervicovaginal fluid for the identification of biomarkers for pathologies of the female genital tract. Proteome Sci. 2010; 8: 63.
  6. Solomon D., Nayar R., eds. The Bethesda system for reporting cervical cytology: definitions, criteria and explanatory notes. 2nd ed. New York, NY: Springer; 2004: 169-75.
  7. Стародубцева Н.Л., Бугрова А.Е., Кононихин А.С., Вавина О.В., Широкова В.А., Наумов В.А., Гаранина И.А., Лагутин В.В., Попов И.А., Логинова Н.С., Ходжаева З.С., Франкевич В.Е., Николаев Е.Н., Сухих Г.Т. Возможность прогнозирования и диагностики преэклампсии по пептидному профилю мочи. Акушерство и гинекология. 2015; 6: 46-52. [Starodubtseva N.L., Bugrova A.E., Kononikhin A.S., Vavina O.V., Shirokova V.A., Naumov V.A., Garanina I.A., Lagutin V.V., Popov I.A., Loginova N.S., Khodzhaeva Z.S., Frankevich V.E., Nikolaev E.N., Sukhikh G.T. Possibility for the prediction and early diagnosis of preeclampsia from the urinary peptide profile. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2015; 6: 46-52. (in Russian)]
  8. Starodubtseva N.L., Kononikhin A.S., Bugrova A.E., Chagovets V., Indeykina M., Krokhina K.N., Nikitina I.V., Kostyukevich Y.I., Popov I.A., Larina I.M., Timofeeva L.A., Frankevich V.E., Ionov O.V., Degtyarev D.N., Nikolaev E.N., Sukhikh G.T. Investigation of urine proteome of preterm newborns with respiratory pathologies. J. Proteomics. 2016; 149: 31-7. doi: 10.1016/j.jprot.2016.06.012.
  9. Бурменская О.В., Назарова Н.М., Прилепская В.Н., Мзарелуа Г.М., Бестаева Н.В, Трофимов Д.Ю., Сухих Г.Т. Прогнозирование риска развития и прогрессирования цервикальных интраэпителиальных неоплазий, ассоциированных с папилломавирусной инфекцией. Акушерство и гинекология. 2016; 2: 92-98. http://dx.doi.org/10.18565/aig.2016.2.92-98
  10. Serce N.B., Boesl A., Klaman I., von Serényi S., Noetzel E., Press M.F. et al. Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis. BMC Cancer. 2012; 12: 597. doi: 10.1186/1471-2407-12-597.
  11. Preston-Martin S., Pike M.C., Ross R.K., Jones P.A., Henderson B.E. Increased cell division as a cause of human cancer. Cancer Res. 1990; 50(23): 7415-21.
  12. Klug A. The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annu. Rev. Biochem. 2010; 79: 213-31. doi: 10.1146/ annurev-biochem-010909-095056.
  13. Wicki R., Marenholz I., Mischke D., Schafer B.W., Heizmann C.W. Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21. Cell Calcium. 1997; 20(6): 459-64. doi: 10.1016/S0143-4160(96)90087-1.
  14. Ahrens T.D., Timme S., Ostendorp J., Bogatyreva L., Hoeppner J., Hopt U.T. et al. Response of esophageal cancer cells to epigenetic inhibitors is mediated via altered thioredoxin activity. Lab. Invest. 2016; 96(3): 307-16. doi: 10.1038/ labinvest.2015.148.
  15. Huber M., Siegenthaler G., Mirancea N., Marenholz I., Nizetic D., Breitkreutz D. et al. Isolation and characterization of human repetin, a member of the fused gene family of the epidermal differentiation complex. J. Invest. Dermatol. 2005; 124(5): 998-1007.
  16. Zhang H., Zhang Y., Zhao H., Niyaz H., Liu P., Zhang L. et al. HPV infection and prognostic factors of tongue squamous cell carcinoma in different ethnic groups from geographically closed cohort in Xinjiang, China. Biochem. Res. Int. 2016; 2016: 7498706. doi: 10.1155/2016/7498706.
  17. Wang C., Zhang Y., Guo K., Wang N., Jin H., Liu Y., Qin W. Heat shock proteins in hepatocellular carcinoma: Molecular mechanism and therapeutic potential. Int. J. Cancer. 2016; 138(8): 1824-34. doi: 10.1002/ ijc.29723.
  18. Tokunaga M., Baron B., Kitagawa T., Tokuda K., Kuramitsu Y. Active hexose-correlated compound down-regulates heat shock factor 1, a transcription factor for HSP27, in gemcitabine-resistant human pancreatic cancer cells. Anticancer Res. 2015; 35(11): 6063-7.
  19. Lin Z., Xiong L., Zhou J., Wang J., Li Z., Hu H., Lin Q. 1y-Glutamylcyclotransferase knockdown inhibits growth of lung cancer cells through G0/G1 phase arrest. Cancer Biother. Radiopharm. 2015; 30(5): 211-6. doi: 10.1089/ cbr.2014.1807.

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Este site utiliza cookies

Ao continuar usando nosso site, você concorda com o procedimento de cookies que mantêm o site funcionando normalmente.

Informação sobre cookies