Association Between The Promoter Of SOX1,DBC1 And ZNF582 Genes Methylation In Cervical Cancer Of Uigur Women In Xinjiang

Objective: This study aimed to explore the promoter of SOX1, DBC1 and ZNF582 genes methylation status and the relationship with high-risk HPV16/18 infection in cervical tissues of Uygur women in Xinjiang, and analyze the effects of the promoter of SOX1, DBC1 and ZNF582 genes methylation on genes expression of m RNA level, and evaluate it as a high sensitivity and specificity tool used for cervical cancer screening.Methods: 1. We detected the infection of HPV16/18 in 51 normal cervical tissues or Chronic cervicitis tissues, 35 cervical intraepithelial neoplasia tissues(CIN) and 68 cervical cancer tissues with the polymerase chain reaction(PCR) method. 2. The promoter of SOX1, DBC1 and ZNF582 genes methylation in above-mentioned tissues was detected by the methylation-specific PCR(MSP) method, and analyzing the correlation between the promoter of SOX1, DBC1 and ZNF582 genes methylation and HPV16/18 infection. 3. The genes expression of m RNA level in SOX1, DBC1 and ZNF582 genes was measured by Quantitative Real-time PCR(q RT-PCR) in 10 methylation-negative normal cervical tissues and 10 methylation-positive cervical cancer tissues.Results: 1. The infection rates of HPV16 in normal cervical tissues or Chronic cervicitis tissues, CIN tissues and cervical cancer tissues were 19.6%, 34.3% and 64.7%, respectively and the infection rates of HPV18 were 2.0%, 8.6%, 13.2%, respectively. 2. The methylation rates of SOX1 gene in normal cervical tissues or Chronic cervicitis tissues, CIN tissues and cervical cancer tissues were 9.8%, 31.4%, 79.4%, respectively. The differences among the three groups were statistically significant(P<0.05); The methylation rates of DBC1 gene in above-mentioned tissues were 21.6%, 40.0 %, 85.3%, normal and CIN tissues compared with cervical cancer tissues, the difference was statistically significant(P<0.01); The methylation rates of ZNF582 gene in above-mentioned tissues were 17.6%, 45.7%, 73.5%, the differences among the three groups were statistically significant(P<0.01). 3. In 93 high-grade squamous intraepithelial lesions(CINII and CINIII) and cervical cancer tissues, The methylation rates of SOX1, DBC1 gene was significantly different in HPV16/18 infection positive group and in negative group(P< 0.05). 4. The genes expression of SOX1, DBC1 and ZNF582 genes in 10 methylation-positive cervical cancer tissues was significantly lower than that in the 10 methylation-negative normal cervical tissues(P<0.01). 5. The promoter of SOX1 gene methylation is high specificity with 86.9%; The promoter of DBC1 gene methylation showed high sensitivity with 76.3%; The sensitive and specificity of the promoter of ZNF582 gene methylation were 69.9% and 83.6%. All of three genes in sensitivity and specificity were higher than that in HPV16/18 infection(61.3%, 82.0%).Conclusion: The promoter of SOX1, DBC1 and ZNF582 genes methylation is associated with cervical cancer of Uygur women in Xinjiang and it may be as molecular markers for early diagnosis of cervical cancer; The promoter of SOX1, DBC1 genes methylation may be associated with HPV16/18 infection; The promoter of SOX1, DBC1 and ZNF582 genes methylation decreased genes expression of m RNA level and it is possible to tumorigenesis of cervical cancer.