| Objective:1.Screening out the differentially expressed mi RNAs of chemotherapy resistance in DLBCL patients;2.Predict the function of differentially expressed mi RNAs target genes and the signaling pathways involved;3.Find therapeutic targets for reversing drug resistance.Methods:1.Collect the clinical data of 30 patients with chemotherapy-sensitive DLBCL and 30 patients with chemotherapy-resistant DLBCL who were confirmed by histopathology in Bethune Hospital of Shanxi Province from March 2021 to August 2022;2.Serum samples from chemotherapy-sensitive group and chemotherapy-resistant group were collected.3.Identification of serum exosomes;4.Five cases in the chemotherapy-sensitive group and the chemotherapy-resistant group were selected for high-throughput sequencing to screen the differentially expressed mi RNAs of chemotherapy resistance in the serum of DLBCL patients,and predict the target genes of mi RNAs with obvious differences;5.Conduct functional research on target genes,and systematically analyze significant functions and signaling pathways;6.SPSS 26.0 software was used for data analysis.The differential expression exocrine mi RNA in serum samples was analyzed by R language software package,and the expression quantity was calculated.The differentially expressed mi RNA was identified by Poisson distribution,Fisher exact test and likelihood ratio test.Results:1.A total of 10 serum samples were collected for initial diagnosis of DLBCL and chemotherapy resistance.After exosome identification and high throughput sequencing,79 mi RNAs related to DLBCL chemotherapy resistance were obtained,of which,42 mi RNAs were highly expressed,and 37 mi RNAs were low in expression;2.The top 11 mi RNAs with obvious differential expression were screened out,hsami R-155-5p、hsa-mi R-424-3p、hsa-mi R-576-5p、hsa-mi R-584-5p、hsa-mi R-3689f、novelhsa-mi R115-5p 、 novel-hsa-mi R80-5p 、 hsa-mi R-12136 、 hsa-mi R-323a-5p 、 novel-hsami R292-5p、hsa-mi R-574-5p;3.Target gene prediction and biological analysis such as pathway and GO were conducted to find out the significant functional changes and enrichment signaling pathway prediction.The results suggested that the target genes were mainly concentrated in the intracellular and intimal systems,and participated in important biological processes such as drug metabolism,intracellular signaling pathways,and the regulation of cell proliferation,thereby exerting biological functions such as redox activity and transcriptional co-activation factor activity.KEGG analysis indicated that the most significant pathway was drug metabolism-cytochrome P450 pathway.By analyzing the target genes in this pathway,we found that mi R-584-5p targeted CYP genes in this pathway,and we speculated that it might play a role through this pathway.Conclusion:1.The exosomes mi R-155-5p and mi R-584-5p are involved in DLBCL resistance.2.DLBCL resistance-related signaling pathways: drug metabolism-cytochrome P450 pathway and intra-tumor signaling pathway.3.It is speculated that mi R-584-5p carried by exosomes is involved in the metabolism of CYP,and knocking out mi R-584-5p may reverse the resistance of DLBCL. |
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