Research On Breast Cancer Tumor Macrophage Related Genes Mining And Its Mechanism

Objective:Breast cancer is the most common cancer in women worldwide and one of the leading causes of cancer-related deaths.In breast cancer,tumor-associated macrophages(TAM)can be abundant and may account for more than 50% of the total number of tumor cells.Studies have shown that TAM is closely related to the poor prognosis of breast cancer,and TAM will affect the therapeutic effect of conventional therapies(such as chemotherapy and radiation therapy)and immunotherapy.Therefore,reducing macrophage infiltration,inhibiting the signaling pathways involved,or interrupting the interaction between TAM and tumor cells may be potential targets in breast cancer treatment.This study combines immune infiltration and weighted network co-expression analysis(Weighted Gene Co-expression Network Analysis,WGCNA)to identify core node genes associated with breast cancer TAM and provide new ideas for breast cancer diagnosis and treatment.Methods:1.Breast cancer microarray data comes from the GEO(Gene Expression Omnibus)database,and the affy package in R language is used to standardize the microarray data.Upload the standardized gene expression data to CIBERSORT and calculate the relative proportion of 22 infiltrating immune cells as the clinical phenotype.2.Combine the analysis of the proportion of infiltrating immune cells with the genetic module of WGCNA to screen the genetic module with the highest correlation with breast cancer TAM.Then combine the degree and differential expression of the node genes to find the core node genes(hub genes)of the weighted co-expression network.3.Use the KM(Kaplan-Meiersurvivalestimate)method to perform a survival analysis of the hub gene to find out the hub genes related to the survival prognosis of breast cancer.4.Expression of Hub Gene in Breast Cancer Using TCGA Database and Breast Cancer Tissue.Results:1.Analysis of immune infiltration of TCGA breast cancer revealed that Macrophages M1 with low infiltration and Macrophages M2 with high infiltration were significantly associated with poor survival prognosis of breast cancer patients.2.The combined analysis of immune infiltration and WGCNA resulted in a tan module that was significantly related to M1 and a turquoise module that was significantly related to M2.The turquoise module gene was significantly related to the development of breast cancer(the correlation was 0.83,P<1e-200).Based on the degree and differential expression of node genes,a total of 14 hub genes were screened out,of which 8 hub genes were in the tan module and 6 hub genes were in the turquoise module.Combined with prognostic analysis of survival,4 hub genes related to poor prognosis of breast cancer were finally screened,namely ISG15,SEMA3 G,CDO1 and GPD1.3.Through real-time quantitative PCR experiments,we verified the experimental results of bioinformatics analysis.The expressions of ISG15,SEMA3 G,CDO1,and GPD1 in breast cancer tissues are consistent with our analysis.Combined with literature reports,it is shown that ISG15,SEMA3 G,CDO1,and GPD1 may play a key role in the occurrence and development of breast cancer TAM.We need further experimental research.