World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website https://wjon.elmerpub.com

Original Article

Volume 16, Number 1, February 2025, pages 120-130


VEGFA Gene Expression in Breast Cancer Is Associated With Worse Prognosis, but Better Response to Chemotherapy and Immunotherapy

Figures

↓  Figure 1. Survival relevance for VEGFA expression. Kaplan-Meier curve with log-rank P value of disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) in TCGA and METABRIC and OS in SCAN-B. The median value was used as a cutoff for two VEGFA expression groups, low (blue) and high (red). VEGFA: vascular endothelial growth factor-A; SCAN-B: Sweden Cancerome Analysis Network-Breast; METABRIC: Molecular Taxonomy of Breast Cancer International Consortium; TCGA: The Cancer Genome Atlas.
Figure 1.
↓  Figure 2. The association between VEGFA expression and clinical parameters. Boxplots of clinical factors: subtype, stage, lymph node metastasis, and distant metastasis in TCGA, METABRIC and SCAN-B cohorts by VEGFA expression. ER: estrogen receptor; HER2: human epidermal growth factor receptor 2; VEGFA: vascular endothelial growth factor-A; SCAN-B: Sweden Cancerome Analysis Network-Breast; METABRIC: Molecular Taxonomy of Breast Cancer International Consortium; TCGA: The Cancer Genome Atlas.
Figure 2.
↓  Figure 3. Association of VEGFA with pathological grade, mutation rates, neoantigens, and cell proliferation-related gene sets. (a) Boxplots of pathological grade and Ki67 gene (MKI67) expression in TCGA, METABRIC, and SCAN-B cohorts. (b) Enrichment score plots of cell proliferation-related gene sets: mitotic spindle, G2M checkpoint, E2F targets, MYC targets v1 and v2, and MTORC1 signaling in TCGA, METABRIC, and SCAN-B cohorts by GSEA using NES (normalized enrichment score) and FDR (false discovery rate). As recommended by GSEA software, FDR < 0.25 defined statistical significance. (c) Boxplots of homologous recombination defects (HRD), intratumor heterogeneity, and the mutation-related scores: silent and non-silent mutation rate, single nucleotide variation (SNV) and indel neoantigens in TCGA cohort. High and low VEGFA expression groups were determined by median cutoff. VEGFA: vascular endothelial growth factor-A; SCAN-B: Sweden Cancerome Analysis Network-Breast; METABRIC: Molecular Taxonomy of Breast Cancer International Consortium; TCGA: The Cancer Genome Atlas; GSEA: gene set enrichment analysis; ITH: intratumor heterogeneity.
Figure 3.
↓  Figure 4. Infiltration fractions of immune cells in the tumor microenvironment by VEGFA expression. Box plots show infiltration fractions for immune cells: CD8+ T cells, CD8+ Tcm cells, CD4+ T cells, CD4+ naive T cells, helper T type 1 (Th1 cells), dendric cells (DC), regulatory T cells (Tregs), helper T type 2 (Th2) cells, B cells, naive B cells, and plasma cells in TCGA, METABRIC, and SCAN-B cohorts by low and high VEGFA expression groups determined by median cutoff. VEGFA: vascular endothelial growth factor-A; SCAN-B: Sweden Cancerome Analysis Network-Breast; METABRIC: Molecular Taxonomy of Breast Cancer International Consortium; TCGA: The Cancer Genome Atlas.
Figure 4.
↓  Figure 5. VEGFA association with angiogenesis and angiogenesis-related data. (a) Boxplots of infiltration fractions for angiogenesis-related cells: pericytes, endothelial cells, microvascular endothelial (MVE) cells, and lymphatic endothelial cells (LECs) in in TCGA, METABRIC, and SCAN-B cohorts. (b) Enrichment score plots of angiogenesis gene set by VEGFA high and low groups by GSEA in TCGA, METABRIC, and SCAN-B cohorts. VEGFA: vascular endothelial growth factor-A; SCAN-B: Sweden Cancerome Analysis Network-Breast; METABRIC: Molecular Taxonomy of Breast Cancer International Consortium; TCGA: The Cancer Genome Atlas.
Figure 5.
↓  Figure 6. VEGFA association with neoadjuvant therapy patients with pCR. (a) Boxplots for VEGFA expression versus pathological complete response (pCR) and residual disease (RD) response for the immunotherapy treatment (durvalumab/olaparib) group and standard chemotherapy group determined from the ISPY2 cohort. (b) Boxplots for VEGFA expression versus pCR and RD response for anthracycline- and taxane-based chemotherapy in neoadjuvant cohorts GSE25066, GSE20194, GSE163882, and GSE34138. VEGFA: vascular endothelial growth factor-A; ER: estrogen receptor; HER2: human epidermal growth factor receptor 2; TNBC: triple-negative breast cancer; NS: not significant.
Figure 6.