Cardiovascular-oncogenic gene crosstalk in breast cancer: Survival, prognosis and therapeutic strategies

Figure 3 Schematic representation of integrated analysis of shared genes and molecular pathways in cardiovascular disease progression and breast cancer outcomes. The figure summarizes the molecular pathways and key regulatory genes that contribute to the bidirectional relationship between cardiovascular disease (CVD) and cancer. Central shared genes, including Janus kinase 2, titin, and Tet methylcytosine dioxygenase 2, are associated with both cardiovascular and oncogenic processes and serve as critical nodes linking disease pathogenesis. These genes influence three major biological pathways: (1) Inflammatory signaling, involving cytokines (interleukin-1, tumor necrosis factor-α, interferon-γ), nuclear factor kappa B, hypoxia-inducible factor-1α, and signal transducer and activator of transcription activation; (2) Metabolic regulation, encompassing AMP-activated protein kinase-mediated energy homeostasis, lipid and glucose metabolism, and oxidative stress responses; and (3) Cellular proliferation and survival, including cell-cycle progression, DNA damage responses, epithelial-mesenchymal transition, and angiogenesis. These pathways converge to promote chronic inflammation and oxidative stress, representing common mechanistic links between CVD and cancer. Key molecular regulators linking CVD and cancer include bromodomain-containing protein 4, dual-specificity tyrosine-phosphorylation-regulated kinase 1B, wingless-related integration site/β-catenin-SRY-Box transcription factor 17 signaling, G protein-coupled receptor kinase 4, AMP-activated protein kinase, peroxisome proliferator-activated receptor-γ, and plasminogen activator inhibitor-1, which collectively regulate cellular proliferation, metabolism, fibrosis, angiogenesis, vascular remodeling, and therapeutic resistance. The convergence of these pathways results in common pathological outcomes, including chronic inflammation, oxidative stress, uncontrolled cellular proliferation, angiogenesis, tissue fibrosis and remodeling, therapy resistance, and disease progression. JAK2: Janus kinase 2; TTN: Titin; TET2: Tet methylcytosine dioxygenase 2; CVD: Cardiovascular disease; CHIP: Clonal hematopoiesis of indeterminate potential; CAD: Coronary artery disease; IL-1: Interleukin-1; TNF-α: Tumor necrosis factor-alpha; IFN-γ: Interferon-gamma; NF-κB: Nuclear factor kappa B; HIF-1α: Hypoxia-inducible factor-1 alpha; STAT: Signal transducer and activator of transcription; AMPK: AMP-activated protein kinase; ROS: Reactive oxygen species; EMT: Epithelial-mesenchymal transition; CRP: C-reactive protein; DNMT3A: DNA methyltransferase 3A; BRD4: Bromodomain-containing protein 4; DYRK1B: Dual-specificity tyrosine-phosphorylation-regulated kinase 1B; Wnt: Wingless-related integration site; SOX17: SRY-Box transcription factor 17; PAH: Pulmonary arterial hypertension; GRK4: G protein-coupled receptor kinase 4; GPCR: G protein-coupled receptor; BP: Blood pressure; PI3K: Phosphoinositide 3-kinase; mTOR: Mechanistic target of rapamycin; p53: Tumor protein p53; PPAR-γ: Peroxisome proliferator-activated receptor gamma; VSMC: Vascular smooth muscle cell; PAI-1: Plasminogen activator inhibitor-1.