ANALYSIS OF APOPTOSIS FACTORS IN PATIENTS WITH PREINVASIVE AND INVASIVE CERVICAL CANCER

This article assesses the disturbance degree of apoptotic program in patients with preinvasive and invasive cervical cancer by investigating the expression level of genes of caspases-3, -6, -8 и -9 in mononuclear cells of periphery blood and in tumor tissue on the two regulating levels – on mRNA lev...

Full description

Bibliographic Details
Main Authors: P. I. Kovchur, E. V. Bachidze, O. V. Kurmyshkina, T. O. Volkova
Format: Article
Language:Russian
Published: ABV-press 2015-04-01
Series:Опухоли женской репродуктивной системы
Subjects:
Online Access:https://ojrs.abvpress.ru/ojrs/article/view/423
_version_ 1826557253095784448
author P. I. Kovchur
E. V. Bachidze
O. V. Kurmyshkina
T. O. Volkova
author_facet P. I. Kovchur
E. V. Bachidze
O. V. Kurmyshkina
T. O. Volkova
author_sort P. I. Kovchur
collection DOAJ
description This article assesses the disturbance degree of apoptotic program in patients with preinvasive and invasive cervical cancer by investigating the expression level of genes of caspases-3, -6, -8 и -9 in mononuclear cells of periphery blood and in tumor tissue on the two regulating levels – on mRNA level (transcriptional) and proteolytic activity (post transcriptional). 75 patients with stage III of cervical intraepithelial neoplasias (CIN) III  (middle age of 32,9 ± 7,4),45 patients with stage IA (31,3 ± 6,0), 21 – with stage II (43,6 ± 13,2), 15 – with stage III–IV (46,9 ± 11,1) have been examined. The control group has been formed from 30 almost healthy donors without any cervical pathology and papilloma human virus (control 1) and 30 patients with a preinvasive and microinvasive cervical cancer (control 2). It has been found that in proportion of progress of cervix cancer, the membranous expression of CD95 increases in MPB – fraction (peripheral blood monocytes) when the a CIN and initial stages of cervix cancer, more than two times. Herewith number CD95+-lymphocytes is positively correlated with stage of cervical cancer (r = 0,91; R2  = 0,82; p << 0,01). It has been found out that the activity gain of caspase-8 (r = 0,92; R2  = 0,86; p << 0,01), caspase-6 (r = 0,77; R2 = 0,59; p << 0,01) and reduction activity of caspase-9 (r = –0,60;  R2 = 0,36; p < 0,01) in mononuclear cells of peripheral blood pointed out on the sensitivity increase to Fas-induced apoptosis. Opposite, in tumor tissue, beginning from CIN stage III, apoptosis-resistant phenotype is formed, it were defined by the expression of caspase-3 (r = –0,72; R2 = 0,52, p < 0,01), caspase-6 (r = –0,59; R2 = 0, 38; p < 0,01) и caspase-9 (r = –0,67; R2 = 0,45; p < 0,01) by mRNA level and proteolytic activity. It has been shown, that the cervical cancer development is accompanied by multilateral disturbances of apoptotic processes, which are realized in decreased function of caspases and multilateral resistance of tumor cells in against signals of apoptosis. The obtained results give an opportunity to examine the genes of caspase as a probable prospective biomarkers in complex diagnostic of a CIN and early diagnosis of a cervical cancer (in combination with morphological criteria and other molecular markers of viral origin)
first_indexed 2024-04-10T01:56:04Z
format Article
id doaj.art-0a0688f4ce3847d2ad1290f1b95ce7cc
institution Directory Open Access Journal
issn 1994-4098
1999-8627
language Russian
last_indexed 2025-03-14T08:25:39Z
publishDate 2015-04-01
publisher ABV-press
record_format Article
series Опухоли женской репродуктивной системы
spelling doaj.art-0a0688f4ce3847d2ad1290f1b95ce7cc2025-03-02T13:05:32ZrusABV-pressОпухоли женской репродуктивной системы1994-40981999-86272015-04-01111616810.17650/1994-4098-2015-1-61-68439ANALYSIS OF APOPTOSIS FACTORS IN PATIENTS WITH PREINVASIVE AND INVASIVE CERVICAL CANCERP. I. Kovchur0E. V. Bachidze1O. V. Kurmyshkina2T. O. Volkova3Petrozavodsk State University; 33 Lenina prospekt, Petrozavodsk, 185910, RussiaN.N. Petrov Oncology Research Institute, Ministry of Health of Russia; 68 Leningradskaya St., Pesochny, Saint Petersburg, 197758, RussiaPetrozavodsk State University; 33 Lenina prospekt, Petrozavodsk, 185910, RussiaPetrozavodsk State University; 33 Lenina prospekt, Petrozavodsk, 185910, RussiaThis article assesses the disturbance degree of apoptotic program in patients with preinvasive and invasive cervical cancer by investigating the expression level of genes of caspases-3, -6, -8 и -9 in mononuclear cells of periphery blood and in tumor tissue on the two regulating levels – on mRNA level (transcriptional) and proteolytic activity (post transcriptional). 75 patients with stage III of cervical intraepithelial neoplasias (CIN) III  (middle age of 32,9 ± 7,4),45 patients with stage IA (31,3 ± 6,0), 21 – with stage II (43,6 ± 13,2), 15 – with stage III–IV (46,9 ± 11,1) have been examined. The control group has been formed from 30 almost healthy donors without any cervical pathology and papilloma human virus (control 1) and 30 patients with a preinvasive and microinvasive cervical cancer (control 2). It has been found that in proportion of progress of cervix cancer, the membranous expression of CD95 increases in MPB – fraction (peripheral blood monocytes) when the a CIN and initial stages of cervix cancer, more than two times. Herewith number CD95+-lymphocytes is positively correlated with stage of cervical cancer (r = 0,91; R2  = 0,82; p << 0,01). It has been found out that the activity gain of caspase-8 (r = 0,92; R2  = 0,86; p << 0,01), caspase-6 (r = 0,77; R2 = 0,59; p << 0,01) and reduction activity of caspase-9 (r = –0,60;  R2 = 0,36; p < 0,01) in mononuclear cells of peripheral blood pointed out on the sensitivity increase to Fas-induced apoptosis. Opposite, in tumor tissue, beginning from CIN stage III, apoptosis-resistant phenotype is formed, it were defined by the expression of caspase-3 (r = –0,72; R2 = 0,52, p < 0,01), caspase-6 (r = –0,59; R2 = 0, 38; p < 0,01) и caspase-9 (r = –0,67; R2 = 0,45; p < 0,01) by mRNA level and proteolytic activity. It has been shown, that the cervical cancer development is accompanied by multilateral disturbances of apoptotic processes, which are realized in decreased function of caspases and multilateral resistance of tumor cells in against signals of apoptosis. The obtained results give an opportunity to examine the genes of caspase as a probable prospective biomarkers in complex diagnostic of a CIN and early diagnosis of a cervical cancer (in combination with morphological criteria and other molecular markers of viral origin)https://ojrs.abvpress.ru/ojrs/article/view/423cervical cancerearly diagnosescaspases-3-6-8-9 expression activityapoptosis-resistant phenotypefas-induced
spellingShingle P. I. Kovchur
E. V. Bachidze
O. V. Kurmyshkina
T. O. Volkova
ANALYSIS OF APOPTOSIS FACTORS IN PATIENTS WITH PREINVASIVE AND INVASIVE CERVICAL CANCER
Опухоли женской репродуктивной системы
cervical cancer
early diagnoses
caspases-3
-6
-8
-9 expression activity
apoptosis-resistant phenotype
fas-induced
title ANALYSIS OF APOPTOSIS FACTORS IN PATIENTS WITH PREINVASIVE AND INVASIVE CERVICAL CANCER
title_full ANALYSIS OF APOPTOSIS FACTORS IN PATIENTS WITH PREINVASIVE AND INVASIVE CERVICAL CANCER
title_fullStr ANALYSIS OF APOPTOSIS FACTORS IN PATIENTS WITH PREINVASIVE AND INVASIVE CERVICAL CANCER
title_full_unstemmed ANALYSIS OF APOPTOSIS FACTORS IN PATIENTS WITH PREINVASIVE AND INVASIVE CERVICAL CANCER
title_short ANALYSIS OF APOPTOSIS FACTORS IN PATIENTS WITH PREINVASIVE AND INVASIVE CERVICAL CANCER
title_sort analysis of apoptosis factors in patients with preinvasive and invasive cervical cancer
topic cervical cancer
early diagnoses
caspases-3
-6
-8
-9 expression activity
apoptosis-resistant phenotype
fas-induced
url https://ojrs.abvpress.ru/ojrs/article/view/423
work_keys_str_mv AT pikovchur analysisofapoptosisfactorsinpatientswithpreinvasiveandinvasivecervicalcancer
AT evbachidze analysisofapoptosisfactorsinpatientswithpreinvasiveandinvasivecervicalcancer
AT ovkurmyshkina analysisofapoptosisfactorsinpatientswithpreinvasiveandinvasivecervicalcancer
AT tovolkova analysisofapoptosisfactorsinpatientswithpreinvasiveandinvasivecervicalcancer