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


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Abstract

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.

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About the authors

Nataliia Leonidovna 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 Mirzoevna Nazarova

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

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

Maka Djemalovna Zardiashvili

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

Email: z-m-d@mail.ru
PhD student

Olga Vladimirovna Bourmenskaya

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

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

Anna Evgenievna 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 Viktorovich 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 Sergeevich 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 Yur’evich 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 Evgenievich 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 Tikhonovich 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

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