Analysis Of The Correlation Between The Expression Of B Cell Receptor Heavy Chain And Light Chain Related Genes And Drug Sensitivity Of Triple Negative Breast Cancer Based On Bioinformatics

Objective: Breast cancer has become the most common malignancy in women worldwide.In the occurrence and development of breast cancer,the adaptive immune system plays an important role in tumor immunity,and B lymphocytes(B cells)in the adaptive immune system can play both anti-tumor and pro-tumor roles.In breast cancer,B cells promote anti-tumor effect by inducing antibody-dependent cell-mediated cytotoxicity(ADCC)mediated by natural killer cells(NK)or activating T cells,and B cells can also inhibit tumor immunity by inducing angiogenesis and secreting antiinflammatory cytokines such as IL-10 and TGF-β.In this paper,we analyzed the expression of heavy chain VDJ gene(IGH),light chain VJ gene,and C gene(IGL and IGK)in B cell receptor(BCR)by combining single cell RNA sequencing(scRNA-seq)and bulk RNA sequencing(bulk RNA-seq).We analyzed the expression of BCR heavy chain and light chain genes in primary tumor tissues,metastatic tumor tissues and different types of breast cancer,then further analyzed the correlation between the expression of BCR genes and the sensitivity to different treatments in triple negative breast cancer(TNBC).We hope to provide clues for the role of B cells in breast cancer and its impact on therapy.Method: Patients gene expression data,including bulk RNA-seq and scRNA-seq data,were downloaded from Gene Expression Omnibus(GEO)and The Cancer Genome Atlas database(TCGA).B cells were isolated from bulk RNA-seq data using CIBERSORT(cell-type identification by estimating relative subsets of RNA transcripts)and from scRNA-seq data by high expression of CD45,CD20,and CD79 A by R(version 4.0.5).Using "Heatmap" R package and “gplot” R package to draw the heat map of BCR genes expression to visually see the gene expression level,using " Arch R" R package to perform transcription factor enrichment analysis,and using“Survminer” R package and "Survival" R package to perform Kaplan-Meier survival analysis on the survival data of breast cancer patients in TCGA database.Results: In metastatic tissues of breast cancer,we found that BCR heavy and light chain related genes were overexpressed in lymph node,and B cells in metastatic lymph node overexpressed CUX1 gene,which promoted tumor metastasis and invasion.Compared with other subtypes,TNBC had a significantly higher expression of BCR heavy and light chain genes and a poor prognosis.The high expression of BCR genes in B cells of TNBC patients was more sensitive to chemotherapy,and TNBC patients could benefit from immunotherapy combined with chemotherapy whether or not they responded.Conclusion: This study used bioinformatics methods,combined with scRNA-seq and bulk RNA-seq data to analyze the correlation between the expression of BCR genes and treatment of triple negative breast cancer.It was found that the high expression of BCR genes in TNBC patients was sensitive to chemotherapy and easy to respond,and TNBC patients could benefit from it whether they responded to immunotherapy combined with chemotherapy or not.