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Analysis Of Differential Expression Of Blood Circrna In Chemotherapy-sensitive And Chenotherapy-insensitive Triple-negative Breast Cancer Patients

Posted on:2021-01-09Degree:MasterType:Thesis
Country:ChinaCandidate:P J HuFull Text:PDF
GTID:2404330602488633Subject:Clinical medicine
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Objective: Through high-throughput sequencing of blood circRNA in chemotherapy-sensitive and chemotherapy-insensitive triple-negative cancer patients,circRNA molecules with significantly different expressions were screened.The purpose of this study was to find circRNA molecules that may be used to predict the efficacy of chemotherapy for triple-negative breast cancer,then conduct ceRNA analysis and KEGG analysis of the predicted potential downstream mRNA to find signal pathways or target genes that may be associated with the sensitivity to chemotherapy in triple negative breast cancer.Methods: Patients with breast needle mass biopsy diagnosed with triple-negative breast cancer and requiring neoadjuvant chemotherapy should take early morning fasting blood samples before treatment.All patients used TAC regimen?T: docetaxel 75mg/?,iv,d1;A: epirubicin75mg/ ?,iv,d1;C: cyclophosphamide 500mg/ ?,iv,d1?.During neoadjuvant chemotherapy,the tumor was evaluated by Dopplerultrasound before each cycle of chemotherapy,and the product of the maximum transverse diameter and longitudinal diameter of the mass measured by B-ultrasound was used to evaluate the efficacy of chemotherapy in each cycle.After completing neoadjuvant chemotherapy as planned,surgical treatment is taken.According to the postoperative pathological results and the size of the mass change under B-ultrasound evaluation,patients with chemotherapy-sensitive triple-negative breast cancer and chemotherapy-insensitive triple-negative breast cancer were selected.Through high-throughput sequencing of blood circRNA in chemotherapy-sensitive and chemotherapy-insensitive patients,circRNA molecules with significant differences in expression in the blood of chemotherapy-sensitive breast cancer patients and chemotherapy-insensitive breast cancer patients were screened.Real-time quantitative PCR detection was used to find circRNA molecules used to predict the chemotherapy effect of triple negative breast cancer.Perform ceRNA analysis and KEGG analysis of the predicted potential downstream mRNA to find signal pathways or target genes that may be related to chemotherapy sensitivity of triple negative breast cancer.Results: 1.In this paper,high-throughput screening of circRNA gene chips was performed on blood from two groups?treatment-sensitive and treatment-insensitive?of patients with triple-negative breast cancer,and a total of 97 circRNA molecules with significantly differentexpressions were screened?Fold change ? 1.5,P <0.05?,where the up-regulation group contains 57 circRNA molecules and the down-regulation group contains 40 circRNA molecules.Through real-time fluorescent quantitative polymerase chain reaction,it was found that hsacircRNA103762 and hsacircRNA008817 were significantly different in the blood of patients with chemotherapy-sensitive and chemotherapy-insensitive triple-negative breast cancer?P <0.05?.2.Taking into account the fold change and P value,five circRNAs in the up-regulated group were selected for ceRNA analysis and subsequent KEGG analysis,found HLA-DMB,IL5,NFKBIB,ADRA1 B,CACNA1S,P2RX2,SLC25A5,SLC26A6,TF,CSNK2 B,RACK1,CTTN and other genes involved in signal pathways were significantly enriched,of which HLA-DMB,IL5,NFKBIB are located on the differentiation pathways of helper T cells 1?Th1?and helper T cells 2?Th2?.Four circRNAs in the down-regulated group were selected for ceRNA analysis and subsequent KEGG analysis.CYP3A5,HSD17B2,UGT2B10,UGT2B7,OR2G2,OR4C5,OR4C6,OR4X1,OR51T1,OR6C2,MT1HL1,MT2 A,DYNC2H1,PFN3 and other genes were found Signal pathways are significantly enriched,of which CYP3A5,HSD17B2,UGT2B10,UGT2B7 are located on the steroid hormone biosynthesis pathway.Conclusion: 1.HsacircRNA103762 and hsacircRNA008817may be used as blood markers for chemotherapy sensitivity of triple-negative breast cancer.2.HSD17B2 and its steroid hormone biosynthesis pathway and POLD2 may be related to chemotherapy sensitivity of triple-negative breast cancer.
Keywords/Search Tags:Triple negative breast cancer, circRNA, Sensitive to chemotherapy, Insensitivity to chemotherapy
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