The Expression And Significance Of Cytokines And Their Receptors In Cervical Lesions

Purpose:1.To explore changes in cervical cytokine levels of women with persistent human papilloma virus(HPV)infection and determine the value of cytokine detection in assessing cervical lesions.2.The IL-6R and the pathway protein pSTAT downstream of IL-6 were further studied,and the roles of IL-6R and pSTAT in the progression of cervical lesions and carcinogenesis were analyzed.Methods:1.We enrolled 146 patients;117 had long-term high-risk(HR)HPV infection(>6months),and 29 were HPV-negative with previous HR-HPV infection.According to histopathological examination,43 patients were diagnosed with cervicitis;35,with low-grade squamous intraepithelial lesions(LSILs);and 39,with high-grade squamous intraepithelial lesions(HSILs).Cytokine levels in vaginal fluid were examined using cytometric bead array,and the values of interleukin(IL)-6 and IL-2levels were converted to a cytokine score.The performance of the cytokine score for diagnosis and risk assessment was compared with that of ThinPrep cytology tests(TCTs).2.We selected 16 patients in the NSIL and LSIL group and 16 patients in the HSIL group which were in the first part of the experiment.We also selected 16 patients with cervical cancer(from IA2 to IB1)hospitalized in our hospital from November 2015 to June 2016.The changes of IL-6,IL-6R and pSTAT expression in patients were analyzed by immunofluorescence and correlation analysis was performed to evaluate the relationship between the three and their effects on cervical lesions.Results:1.Disease severity was positively associated with IL-6 levels and inversely related to IL-2 levels.2.The area under the curve(AUC)was higher for the cytokine score including IL-6 and IL-2 than for TCTs for HSILs.Comparisons of the sensitivity,specificity,Youden index,and positive and negative predictive values for HSILs demonstrated that the cytokine score was better than TCT.3.HPV-positive patients with high cytokine scores showed increased risk of developing HSIL within 3 years.The hazard ratio for the cytokine score was 3.12;thus,the risk of developing HSIL was related to the cytokine score.4.The expressions of IL-6R and pSTAT were correlated with the severity of cervical lesions.The correlation coefficients were R=0.73 and R=0.57(P<0.05),respectively.5.IL-6R and pSTAT3 increased with the increase in IL-6 expression.However,through stratification analysis,there was a difference between the them.There was a significant correlation between the expression of pSTAT3 and IL-6 among different grades of cervical lesions and cervical cancer.However,for IL-6R,after stratified analysis,the correlation with IL-6 expression was not obvious.Conclusions:1.Disease severity was positively associated with IL-6 levels and inversely related to IL-2 levels.2.The cytokine score increased with the severity of cervical lesions and could distinguish more patients from HPV-positive women3.The cytokine score can be used to predict the risk of disease progression.4.Carcinogenesis of the cervical epithelium can lead to the expression of IL-6R on the surface of its cell membrane,and its expression level gradually increases with the degree of canceration.5.There is a clear correlation between IL-6 and pSTAT3,but its correlation with IL-6R on the cell membrane surface is still unable to draw accurate conclusions,which needs further study.