| Background and Objective:cervical cancer is a serious threat to women's health,especially in some less developed countries and regions.The incidence and mortality of cervical cancer rank as second in female patients,and persistent infection with high-risk HPV is the main cause of cervical cancer.Patients with high-risk HPV infections undergo low-grade intraepithelial neoplasia,high-grade intraepithelial neoplasia,and ultimately develop invasive cervical cancer.At present,persistent high-risk HPV infection and different grades of cervical intraepithelial neoplasia caused by the high-risk HPV infections are mainly examination through acetic acid staining and iodine staining under the colposcopy.But colposcopy is an invasive examination,and it need complete by doctors,so it is may result in misdiagnosis.Therefore,we need to find a simple,rapid and accurate method to determine the degree of cervical intraepithelial neoplasia.MiRNAs have been found to be abnormally expressed in a variety of malignant tumors and are involved in the occurrence,development,invasion,metastasis,and recurrence of malignant tumors.Different miRNAs play the different roles as tumor suppressor genes or oncogenes.Currently,few of researchers have found the miRNAs,especially miRNA-214,miRNA-34a,miRNA-200a,are abnormally exprssed in plasma of patients either persistently infected by HPV or at different levels of cervical intraepithelial neoplasia.Increased expression of miRNAs-21 was found in cervical cancer tissues and cell lines.miRNA-214 and miRNA-34a were found to be reduced in cervical cancer tissues and/or cell lines,and it is still unclear the role of miRNA-200a played in cervical tissues and cell lines.Therefore,this study focuses on the changes of miRAN-21,214,34a,and 200a in plasma of the persistent high-risk HPV infection,the different grades of cervical intraepithelial neoplasia and cervical cancer.It may provide a evidence-based medicine for finding different grades of cervical intraepithelial neoplasia and cervical cancer.METHODS:According to the inclusion criteria of the trial,venous blood was collected from 232 patients,then it was centrifugated and detected the changes of miRNA-21,214,34a,and 200a in plasma by qRT-PCR,all of them,including 42 cases were the normal control group.31 cases were persistent high-risk HPV infection,19 cases were cervical intraepithelial neoplasia grade 1(CIN1),54 cases were cervical intraepithelial neoplasia grade 2(CIN2),71 cases were cervical intraepithelial neoplasia grade 3(CIN3),15 cases were cervical cancer(CC).Besides,the levels of tissues miRNA-21,miRNA-214,miRNA-34a and miRNA-200a was determined from formalin-fixed,paraffin-embedded tissues that are diagnosed by pathology of 63 patients included above,who were 8 cases out of the CIN1 group,29 cases out of the CIN2 group,and 26 cases out of the CIN3 group.The X2 test was used to analyze the questionnaire survey among the persistent high-risk HPV infection group,the CIN2 and CIN3 groups.The non-paired t-test was used to analyze the levels of miRNA-21,214,34a,and 200a in plasma and formalin-fixed,paraffin-embedded tissues.Kappa test for each miRNA plasma result and cervical tissue results(consistency test).Results:1.The persistent high-risk HPV infection group were respectively compared with CIN2 group,CIN3 group,the difference was statistically significantly in passive smoking(P<0.05),while CIN2 group were compared with CIN3 group,the difference was no statistically significant(P>0.05),and with regard to the other factors,any two groups of comparison,the difference was no statistical significance(P>0.05).2.miRNA-21 in plasma was increasing with the upgrade of cervical intraepithelial neoplasia.The normal control group was respectively compared with CIN2 group,CIN3 group,cervical cancer group,the difference was statistically significantly(P<0.05),The persistent high-risk HPV infection group was respectively compared with CIN2 group,CIN3 group,cervical cancer group,the difference was statistically significantly(P<0.05).Except them,any two groups of comparison,the difference was no statistically significantly(P>0.05).The changes in plasma of CIN1 group,CIN2/3 and cervical cancer group were consistent,and the difference was no statistically significant.There were no statistically significant in CIN1,CIN2,and CIN3 among the cervical tissues(P>0.05),which were consistent with plasma by the Kappa test.3.The level of miRNA-214 in plasma was decreasing with the upgrade of cervical intraepithelial neoplasia,The normal control group was respectively compared with CIN2 group,CIN3 group and cervical cancer group,the difference were statistically significantly(P<0.05).The persistent high-risk HPV infection was respectively compared with CIN2 group,CIN3 group and cervical cancer group,the difference was statistically significantly(P<0.05).and there were no statistical difference between the other groups(P>0.05).The changes in plasma of CIN1 group,CIN2/3 and cervical cancer group were consistent,and the difference was not statistically significant.There were no statistically significant in CIN1,CIN2,and CIN3 among the cervical tissues(P>0.05),which were consistent with plasma by the Kappa test.4.The level of miRNA-34a in plasma was decreasing with the upgrade of cervical intraepithelial neoplasia,The normal control group was respectively compared with CIN2 group,CIN3 group and cervical cancer group,the difference was statistically significantly(P<0.05).The persistent high-risk HPV infection was respectively compared with CIN2 group,CIN3 group,the difference was statistically significantly(P<0.05).and there were no statistical difference between the other groups(P>0.05).The changes in plasma of CIN1 group,CIN2/3 and cervical cancer group were consistent,and the difference were no statistically significant.There were no statistically significant difference in CIN1,CIN2,and CIN3 among the cervical tissues(P>0.05),which were consistent with plasma by the Kappa test.5.The level of miRNA-200a in plasma that was the same as the miRNA-214,34a,was decreasing with the upgrade of cervical intraepithelial neoplasia,The normal control group and persistent high-risk HPV infection group were respectively compared with CIN2 group,CIN3 group and cervical cancer group,the difference was statistically significantly(P<0.05),and there were no statistical difference between the other groups(P>0.05).The changes in plasma CIN1 group,CIN2/3 and cervical cancer group were consistent,and the difference was no statistically significant.There were no statistically significant difference in CIN1,CIN2,and CIN3 among the cervical tissues(P>0.05),which were consistent with plasma by the Kappa test.Conclusion:1.Passive smoking can promote the development of cervical intraepithelial neoplasia which has infected high-risk HPV.2.Levels of miRNA-21,miRNA-214,miRNA-34a,and miRNA-200a in plasma are consistent with changes in cervical tissues.Detection of plasma changes in these miRNAs may indicate cervical high-grade lesions or cervical cancer. |
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