Clinical Characteristics And Prognosis Of Early Cervical Adenocarcinoma And Its Methylation Of Related Genes

Objective: 1.To investigate the relationship between clinicopathological features and prognosis of early Cervical Adenocarcinoma,we retrospectively analyzed 140 cases of Cervical Adenocarcinoma treated in the Tumor Hospital Affiliated to Xinjiang Medical University.2.Screening and preliminary study of methylation sites and genes in Cervical Adenocarcinoma,to determine the expression and distribution of methylation in Cervical Adenocarcinoma cells.3.To analyze the specific expression of SOX1,CCND1 and PRKCA gene methylation in early Cervical Adenocarcinoma tissues,so as to find molecular markers for predicting the occurrence and development of Cervical Adenocarcinoma.Methods: 1.Data of 140 patients with early Cervical Adenocarcinoma(stage?B1-?A2)who underwent radical hysterectomy in the Tumor Hospital Affiliated to Xinjiang Medical University from January 2010 to December 2017 were collected and collated.Univariate and multivariate analysis was performed on the risk factors that might affect the prognosis of Cervical Cancer.2.The methylation of 5 cases of Cervical Adenocarcinoma tissues and 5 cases of normal cervical tissues were analyzed by Illumina850 K methylation chip.The genes with abnormal methylation were screened out and analyzed by GO functional annotation analysis and enrichment analysis of KEGG signal transduction pathways.3.BSP and Q-RT-PCR were used to verify the expression of SOX1,CCND1 and PRKCA in Cervical Adenocarcinoma,Squamous Cell Carcinoma and normal cervical tissues.Results: 1.140 patients with early invasive Cervical Adenocarcinoma(stage?B1-?A2)diagnosed by pathologists after 8 years of operation showed a 5-year tumor-free survival rate of 81.2% and a 5-year overall survival rate of86.7%.The Clinical characteristics of Cervical Adenocarcinoma differs from that of Cervical Squamous Cell Carcinoma.Univariate analysis of early Cervical Adenocarcinoma showed that the risk factors for recurrence within 5 years include vascular thrombus,lymph node metastasis,ovarian metastasis,and the risk factors for death within 5 years included lymph node metastasis,deep interstitial infiltration,vascular embolus,ovarian metastasis,postoperative adjuvant treatment.Multivariate analysisshowed that the independent prognostic factors of recurrence within 5 years were vascular tumor embolus and ovarian metastasis,and the high risk factors of death within 5 years included lymph node metastasis vascular tumor embolus and ovarian metastasis.2.Totally4056 sites showed differential expression in Cervical Adenocarcinoma tissues compared to normal cervical tissues,of which 3738 were hypermethylated,318 were hypomethylated.Most of the hypermethylated CpG loci were located in CpG island,CpG shores and promoter regions,and the body region was the predominant site for the differentially methylated CpG loci.GO functional annotation analysis showed that the differential expressed genes in Cervical Adenocarcinoma tissues were mainly involved in the processes of tumor growth,development,metabolism,ion transport,transcriptional regulation,cell division,cell cycle regulation and signal transduction.KEGG signaling pathway analysis showed that the most significant differential signaling pathway was the neuroactive ligand-receptor interaction.Gene-net-work analysis suggested that CCND1,CTNNB1,MAPK10 and PRKCA were involved in several pathways.3.The quality of the samples is qualified,and the results of all operations are normal.The results of BSP showed that SOX1 was a specific methylation expression gene in Cervical Adenocarcinoma,and there was significant difference among the three groups(P<0.05).PRKCA and CCND1 were not specific methylation expression genes in Cervical Adenocarcinoma,and there was no significant difference(P>0.05).Q-RT-PCR results showed that SOX1,PRKCA in Cervical Adenocarcinoma group and Cervical Squamous Cell Carcinoma group,Cervical Adenocarcinoma group and normal cervical group were statistically significant(P<0.05),CCND1 in Cervical Adenocarcinoma group and normal cervical group,Cervical Squamous Cell Carcinoma group and normal cervical group were statistically significant(P<0.05).Conclusion: 1.Radical resection of cervical cancer is an effective treatment for early cervical adenocarcinoma.For patients with stage?B1-?A2,bilateral ovaries are not recommended.Lymph node metastasis is an important factor affecting the prognosis of cervical adenocarcinoma.In order to improve the prognosis of the patients in endometrial carcinoma,they should be treated by individual therapies.2.DNA methylation genes are specifically expressed in Cervical Adenocarcinoma tissues in Xinjiang.Five of these genes(SOX1?CCND1?PRKCA?CTNNB1 ?MAPK10)that show differential expression may play important regulatory roles in Cervical Adenocarcinoma development through affecting multiple signal pathways associated with Cervical Adenocarcinoma.3.1.Tumor suppressor gene SOX1 is a specific methylation expression gene of Cervical Adenocarcinoma,andhypermethylation of SOX1 promoter region is an important event in the development of Cervical Adenocarcinoma,which is expected to become a specific molecular marker for the diagnosis of Cervical Adenocarcinoma.PRKCA and CCND1 genes can not be proved to be specific methylation expression genes of Cervical Adenocarcinoma.Considering the small sample size and detection sites of BSP,further study is needed.