关键词: 宫颈肿瘤, 白细胞介素17, DNA甲基化, CpG岛, 人乳头瘤病毒16

Abstract: Objective　To investigate the correlation between CpG island methylation of IL-17 gene promoter and cervical cancer,and to provide new ideas for clinical diagnosis and immunotherapy of cervical cancer.Methods　43 cervical cancer patients （cervical cancer group） and 62 patients with precancerous lesions〔23 cases with CINⅠ（CINⅠ group）,39 cases with CINⅡ~Ⅲ（CINⅡ~Ⅲ group）〕 who received treatment in Inpatient Department of Tangshan Gongren Hospital from March 2011 to May 2012 were selected,and another 43 patients who had undergone total abdominal hysterectomy in this hospital at the same period due to uterine fibroids were enrolled as control group.Cervical tissue specimens of patients in four groups were obtained by surgery.DNA in cervical tissue of patients in four group was extracted to make a detection of HPV16 DNA,CpG island methylation status in IL-17 gene promoter was detected by using CpG island methylation specific PCR （MSP）,IL-17 mRNA expression levels were detected by semi-quantitative reverse transcription PCR （RT-PCR）,correlation between CpG island methylation rate of IL-17 gene promoter and IL-17 mRNA expression levels,and the relevance of this rate to the positive rate of HPV16 DNA were analyzed,and CpG island methylation status of IL-17 gene promoter in cervical cancer patients of different ages and clinical features were also analyzed.Results　HPV16 DNA positive rates in four groups were significantly different （P<0.001）.CpG island methylation rate of IL-17 gene promoter in CINⅡ~Ⅲ group and cervical cancer group was significantly lower than that in control group（P<0.01）;CpG island methylation rates of IL-17 gene promoter in CINⅠ group and control group,CINⅠ group,CINⅡ~Ⅲ group,cervical cancer group were not significantly different （P> 0.05）;CpG island methylation rates of IL-17 gene promoter between CINⅠgroup and CINⅡ~Ⅲ group were not significantly different （P>0.05）.The expression levels of IL-17 mRNA in CINⅠ group,CINⅡ~Ⅲ group and cervical cancer group were higher than those in control group （P<0.05）;the expression levels of IL-17 mRNA in CINⅠgroup,CINⅡ~Ⅲ group and cervical cancer group was not significantly different （P>0.05）;the expression level of IL-17 mRNA between CINⅡ~Ⅲ group and cervical cancer group was not significantly different （P>0.05）.According to the detected results of CpG island methylation in IL-17 gene promoter,all patients were divided into patients with CpG island methylation of IL-17 gene promoter （93 cases） and non-methylation patients （55 cases）,IL-17 mRNA expression level of patients with CpG island non-methylation in IL-17 gene promoter was higher than that in methylation patients （P<0.05）.In all patients’ cervical tissues,CpG island methylation rate of IL-17 gene promoter was negatively correlated with its mRNA expression level（rs=-0.627,P<0.05）.There was correlation between CpG island methylation rate of IL-17 gene promoter in all patients’ cervical tissue and infection positive rates of HPV16 DNA （χ2=33.209,P<0.05,r=-0.474）.CpG island methylation rate of IL-17 gene promoter in cervical cancer patients at Ⅱ and Ⅲ clinical stages were lower than that of patients at Ⅰ clinical stage （P<0.05）;CpG island methylation rates of IL-17 gene promoter among cervical cancer patients of different ages,pathological grading,tumor diameter,and with or without lymph node metastasis were not significantly different （P>0.05）.Conclusion　CpG island methylation of IL-17 gene promoter is related with high-risk HPV16 infection,CpG island methylation of IL-17 gene promoter may be associated with the occurrence and development of cervical cancer.

Key words: Uterine cervical neoplasms, Interleukin-17, DNA methylation, CpG islands, Human papillomavirus 16