Association of Matricellular Protein, Growth Factor, and Transcription Factor with Molecular Subtypes of Breast Cancer: A Case Control Study

Background: Breast cancer is a heterogeneous disease comprising molecular subtypes such as Luminal A, Luminal B, Human Epidermal Growth Factor 2 (HER-2)-Enriched, and Triple Negative, each with distinct clinical, molecular, and immunological features. Immunological markers play a critical role in modulating tumor behavior, angiogenesis, and immune evasion. Aim: This study aimed to identify key immunological markers that correlate with the molecular (intrinsic) subtypes of breast cancer and to explore their potential as prognostic factors. Methods: Serum samples from 180 breast cancer patients (56 untreated and 74 treated) were analyzed using Enzyme-Linked Immunosorbent Assay (ELISA) to determine the levels of four immunological biomarkers, including Cellular Communication Network Factor 6/WNT 1 Inducible Signaling Pathway Protein (CCN6/WISP3), Vascular Endothelial Growth Factor A (VEGF-A), Nuclear Factor Kappa B (NF-κB p65), and Cancer Antigen CA15-3. Demographic data and clinical parameters were collected using questionnaires. Results: Compared to the controls, patients with breast cancer exhibited significantly elevated levels of VEGF-A, NF-κB p65, and CA15-3, alongside decreased CCN6 levels (P < 0.05). At the molecular subtype level, HER2-enriched tumors showed the highest concentrations of CCN6 and VEGF-A, while elevated NF-κB p65 and CA15-3 levels were noted in Luminal B tumors, indicating the lowest CCN6 concentration in triple-negative tumors. Conclusions: This study demonstrates the roles of CCN6, VEGF, NF-κB p65, and CA15-3 as reliable biomarkers for distinguishing between molecular subtypes and suggests their potential as prognostic indicators.