ABSTRACT
Objective @#To construct a cell-free DNA ( cfDNA) methylation model for early screening in male pa- tients with gastric cancer by using novel cfDNA methylation detection technology．@*Methods @#Methylation informa- tion of the whole genome of gastric cancer patients were detected by cell-free methylated DNA immunoprecipitation and highthroughput sequencing ( cfMeDIP-seq ) technology and locate gastrogenic cfDNA． Then bioinformation methods were used to extract specific methylation labels which could distinguish GC patients and establish diagnosis model by random forest algorithm. Related validation clinical researches were also conducted. @*Results @#63 most sig- nificant DMR were selected to construct the cfDNA methylation model based on GC samples and normal control samples，the goal sensitivity was above 85 percent while the goal specificity was above 95% ．The sensitivity and specificity of the validation set were 98. 7% and 99. 0% while the area under curve(AUC) was 0. 999．@*Conclusion@#The cfDNA methylation model constructed in this study has good performance in predicting GC.
ABSTRACT
Objective To analyse the change of DNA methylation with 5-Azac injection in acute graft-versus-host dis- ease (aGVHD) mouse model, which received allogeneic bone marrow transplantation, and explore the immunomodulatory ef-fects of 5-Azac. Methods Male C57BL/6 (H-2b)and female BALB/c (H-2d) mice were selected as donor and recipient of complete allotransplantation. BABL/c mice were divided into two groups, transplantation control group and 5-Azac experi-mental group. At 1-7, 14, 21 and 28-day after transplantion, 5-Azac 0.25 mg/kg (0.3 mL/time) was injected by tail vein in experimental group, while the control group were injected with sterile water 0.3 mL/time. Peripheral blood DNA samples were collected from three control mice and three experimental mice, then mixed with equal amount respectively. The MeDIP-seq method was selected to detect methylation changes in mice, and the differential DNA methylation in the biological path-ways was analyzed. Results The survival time was prolonged, and the rejection reaction was decreased in 5-Azac experi-mental group, which suggested immune hyporesponsiveness post aGVHD. The MeDIP-seq result showed that 369 different DNA methylation located in the promoter regions, including 239 up-regulated genes and 130 down-regulated genes. There were 184 differential DNA methylation genes located in the exon regions, including 113 up-regulated genes and 71 down-regulated genes. Differential DNA methylation genes involved in 10 immunological signaling pathways, respectively. Among them, TGF-β, GSK-3β, SYK, PI3K, NFAT, CD28 andα4β7 were closely related to the development of aGVHD. Conclu-sion 5-Azac can effectively induce immune hyporesponsiveness post aGVHD by changing the gene methylation status.