The Clinical Efficacy Of ShuYuSanJie Prescription Combined With ¹²⁵I Seed Implantation In The Treatment Of Breast Cancer And Analysis Of Network Pharmacology Mechanism

Objective1.To evaluate the clinical efficacy of Shu Yu San Jie Prescription combined with ¹²⁵I seed implantation in the treatment of breast cancer by retrospective study and the prognostic factors.2.Based on the network pharmacology method,to explore the mechanism of Shu Yu San Jie Prescription's efficacy in the treatment of breast cancer by analyzing the effective components and the synergistic effects of components.Methods1.The cases were from The First Affiliated Hospital of Tianjin University of TCM oncology'clinical cases during the period of December 1,2013-June 30,2019.The 52 breast cancer patients received ¹²⁵I radioactive particles implantation treatment combined with Shu Yu San Jie Prescription.The patients were followed up from the time of operation of ¹²⁵I radioactive particles implantation.The end point of follow-up was the date of disease progression,or the date of loss to follow-up,or death.We evaluated the efficacy of the combined treatment of TCM and modern medical technology by compareing the imaging results,efficacy between different syndromes and progression-free survival and prognostic factors.2.The analysis platform of TCMSP database and the Uni Prot Knowledgebase database was used to search effective active ingredients and the targets.Through Therapeutic Target Database and Gene cards Database got breast cancer related targets.Using Venny 2.1.0 tool draw the venn map and got the common targets of Shu Yu San Jie Prescription and breast cancer.The protein interaction map was obtained from String database.Cytoscape 3.2.1 software was used to construct the PPI network diagram of the effective active component-disease-targets-pathway of Shu Yu San Jie Prescription.With the help of DAVID database,GO functional annotation and pathway enrichment analysis were carried out and the mechanism of action of Shu Yu San Jie Prescription in the treatment of breast cancer was further analyzed and discussed.Results1.The local mass control rate at 6 months after surgery:imaging follow-up was conducted for 52patients at 6 months after surgery.According to WHO solid tumor evaluation criteria,13 lesions had complete remission?CR?,32 lesions had partial remission?PR?,4 lesions had stable lesion?SD?,and 3 lesions had progressive lesion?PD?.The control rate of local lesions?CR+PR?was86.5%.2.The different efficacy between TCM syndromes:According to the distribution of syndromes,52 patients were divided into the deficiency syndrome group and the empirical group.According to P=0.932>0.05,there was no statistically significant differences between the two groups.According to the syndrome type distribution,the differences in efficacy between the three groups of the deficiency syndrome group,P=0.633>0.05,indicated that there was no statistically significant difference between the qi-yin deficiency group,the qi-blood deficiency group and the chong-ren disorder group.According to the syndrome type distribution in the three groups of the empirical group,P=0.248>0.05,the results indicated that there was no statistically significant differences between the groups of the qi stagnation and phlegm group,the toxic heat accumulation group and the stasis and stasis syndrome group.3.Progression-free survival:The follow-up time was 12-72 months,and the median follow-up time was 28 months.The 1-year and 2-year progression-free survival rates were 76.9%and51.4%,with a median progression-free survival time of 25 months and an average progression-free survival time of 29.9 months.4.Prognostic factors:Age,BMI,hormone receptor status,clinical stage,presence of distant organ metastasis,combination therapy,preoperative platelet count,tumor marker CA15-3,syndrome differentiation and deficiency in TCM were included in the prognostic analysis.Single factor analysis showed that hormone receptor negative state?P=0.001?,period?P<0.001?,distant organ metastasis?P<0.001?,combination therapy?P<0.001?were related with ¹²⁵I radioactive particles implantation combined with Shu Yu San Jie Prescription.The risk factors with P<0.05in single factor analysis were analyzed by multiple factors.The results showed that the combination of distant organ metastasis?P<0.001?,with other treatments?P=0.004?and period?P=0.012?was the main factor affecting the prognosis.5.Active ingredients of Shu Yu San Jie Prescription:Through database retrieval and screening,a total of 65 kinds of active ingredients were obtained,including 17 species of bupleurum root,5species of fructus aurantii,15 species of curcuma,3 kinds of turmeric,13 kinds of white peony root,7 kinds of chuanxiong,15 kinds of tuckahoe,7 kinds of fritillaria thunbergii and 12 kinds of cat's foot grass.6.Effective components and core targets of Shu Yu San Jie Prescription:Through the screening of effective component target information,a total of 175 corresponding targets were obtained.20components with Degree?15 were selected as the main components and 32 targets with Degree?10 were selected as the core targets.7.The common targets:Through searching the corresponding database,a total of 407 targets of breast cancer-related targets were obtained.There are 13 common targets,respectively:ADRB2?AR?BCL2?CHEK1?ESR1?ESR2?GSK3B?NOS2?NR3C1?PGR?PIK3CG?PPARG?PTGS2.ESR1,PTGS2,NR3C1 and GSK3B were 4 key targets.8.GO functional annotation and the pathway enrichment analysis:GO function analysis by DAVID database,the results showed that the hydrophobic depressive fights party mainly involved in 15 biological processes,such as:transcription initiation from RNA polymerase II promoter,positive regulation of transcription from RNA polymerase II promoter,peptidyl-threonine phosphorylation,cell-cell signaling,steroid hormone mediated signaling pathway,signal transduction,positive regulation of sequence-specific DNA binding transcription factor activity,negative regulation of smooth muscle contraction,negative regulation of cell growth,negative regulation of gene expression,positive regulation of transcription,DNA-templated,transcription,DNA-templated,mammary gland alveolus development,intracellular estrogen receptor signaling pathway,response to drug.The gene targets were concentrated in 7 cell components,such as nucleus,nucleoplasm,cytosol,protein complex,cytoplasm,perinuclear region of cytoplasm,mitochondrial outer membrane.Influences15 molecules such as steroid hormone receptor activity,steroid binding,sequence-specific DNA binding,RNA polymerase II transcription factor activity,ligand-activated sequence-specific DNA binding,enzyme binding,transcription factor activity,sequence-specific DNA binding,protein binding,core promoter sequence-specific DNA binding,transcriptional activator activity,RNA polymerase II core promoter proximal region sequence-specific binding,zinc ion binding,transcription factor binding,ATPase binding,RNA polymerase II transcription factor activity,estrogen-activated sequence-specific DNA binding,beta-catenin binding,RNA polymerase II core promoter proximal region sequence-specific DNA binding.KEGG analysis received 10 significant pathways,including tumor related pathways,prolactin signaling pathway,estrogen signaling pathway,thyroid hormone signaling pathway,adipocyte lipolysis pathway,etc.It was enriched in the signaling pathways associated with small cell lung cancer,prostate cancer and colorectal cancer.Shu Yu San Jie Prescription may exert anti-tumor effect in the treatment of breast cancer by regulating apoptosis,tumor angiogenesis,improving the levels of thyroid hormone,prolactin,estrogen and other related hormones and hormone receptors.