Genetic association of lipids and lipid-lowering drug target genes with breast cancer

Figures

• 

  Fig. 1. Outline of the study design. LDL-C low-density lipoprotein cholesterol, TG triglyceride, HMGCR HMG-CoA reductase, NPC1L1 Niemann-Pick C1-like protein 1, PCSK9 proprotein convertase subtilisin/kexin type 9, ABCG5 ATP-Binding Cassette Subfamily G Member 5, ABCG8 ATP-Binding Cassette Subfamily G Member 8; APOB Apolipoprotein B-100, LDLR LDL Receptor, ANGPTL3 angiopoietin-like 3; APOC3 Apolipoprotein C-III, LPL lipoprotein lipase

• 

  Fig. 2. Association between genetically proxied drug targets and the risk of breast cancer. Forest plot of the association between a 1-mmol/L (LDL-C, 38.7 mg/dL; TG, 88.9 mg/dL) change in the lipid levels of nine lipid-lowering drug targets with breast cancer risk in the discovery dataset (A), and breast cancer risk in the replication dataset (B). Data are represented as ORs with 95% confidence intervals (error bars). An OR of < 1.00 suggests a decreased risk of disease associated with lipid-lowering drug treatment. Associations are significant after correcting for multiple testing (9 genes, p < 0.05/9). LDL-C low-density lipoprotein cholesterol, TG triglycerides, OR odds ratio, HMGCR HMG-CoA reductase, NPC1L1 Niemann-Pick C1-like protein 1, PCSK9 proprotein convertase subtilisin/kexin type 9, APOB Apolipoprotein B-100, ABCG5 ATP-Binding Cassette Subfamily G Member 5, ABCG8 ATP Binding Cassette Subfamily G Member 8; LDLR LDL Receptor, ANGPTL3 angiopoietin-like 3, APOC3 Apolipoprotein C-III; LPL, lipoprotein lipase

• 

  Fig. 3. HMGCR expression levels and prognosis in tumors. A HMGCR expression in different cancers from TIMER2.0. B Immunohistochemistry of HMGCR in BC tissue from HPA platforms. C Demonstrates the Cox Proportional Hazards Regression Analysis of HMGCR Gene Expression versus Overall Survival (OS) in Breast Cancer Patients. Through the survival curve, Hazard Ratio (HR), and p-value, it reveals the potential association between HMGCR expression and OS. D Illustrates the Cox Proportional Hazards Regression Analysis of HMGCR Gene Expression versus Relapse-Free Survival (RFS) in Breast Cancer Patients. By integrating the survival curve, HR, and p-value, it analyzes the intrinsic link between HMGCR expression and RFS. E The relationships between HMGCR, immune score, stromal score, and ESTIMATE score. TCGA, The Cancer Genome Atlas; GTEx, Genotype Tissue Expression Project

• 

  Fig. 4. Correlation between HMGCR expression and immune characteristics A, B Correlation between HMGCR expression and the relative abundance of 24 immune cells. Dot size corresponds to the absolute value of the Spearman correlation coefficient. C Correlation between relative enrichment scores of immune cells (including Tcm cells, Th2 cells, T helper cells, eosinophils, mast cells, pDC cytotoxic cells, B cells, CD8 T cells, DC, T cells, CD56dim cells, aDC, TReg, TFH) and HMGCR expression. Tcm T central memory, Th2 T helper 2, pDC pre-dendritic cells, DC dendritic cells, aDC activated DCs, TReg regulatory T cells, TFH T follicular helper

• 

  Fig. 5. Circular heatmap of the effect of HMGCR inhibitors on immune cell and inflammatory factor phenotypes and the effect of immune cell and inflammatory factor phenotypes on breast cancer. A Effects of HMGCR inhibitors on immune cell phenotype. B Effects of immune cell phenotype on breast cancer. C Effects of HMGCR inhibitors on inflammatory factor phenotype. D Effects of inflammatory factor phenotype on breast cancer. The right-hand parameter represents the p-value for each of the five analyses, which serve to illustrate the degree of significance associated with each. IVW Inverse Variance Weighted, WM Weighted Median, WMODE Weighted mode, SM Simple mode