Evaluation of serum CCN6, VEGF-A, and NF-κB p65 and their clinicopathological correlations in breast cancer

Abstract

Introduction and aim. CCN6, a transcriptional regulator within the CCN family, influences breast tumorigenesis by interacting with key angiogenic (VEGF-A) and inflammatory (NF-κB p65) pathways. This study establishes simultaneous evaluation of these serum biomarkers and comparison with CA 15-3 across untreated and treated breast cancer cohorts. This study aimed to evaluate their serum level and clinicopathological associations to understand their role in tumor progression and potential diagnostic utility. Materials and methods. Serum biomarkers were measured via ELISA in 130 breast cancer patients (56 untreated and 74 treated) and 50 controls. Demographic and clinical data were collected through questionnaire-based interviews and clinicopathological data from medical records. Results. CCN6 had the greatest effect size (F=1.10), followed by NF-κB p65 (F=0.51) and VEGF-A (F=0.22). The diagnostic efficacy (AUC=0.995; p=0.0001), sensitivity (96%), and specificity (100%) of CCN6 were superior to those of CA15-3 (AUC=0.855) and NF-κB p65 (AUC=0.813). Logistic regression demonstrated that downregulated CCN6 was inversely associated with disease outcome (OR=0.440; p=0.0001), whereas elevated NF-κB p65 (OR=1.737) levels increased breast cancer risk. Conclusion. CCN6 showed promising diagnostic performance and exhibits an inverse association with breast cancer, outperforming NF-κB p65 and CA 15-3; these findings underscore CCN6's potential as a preliminary non-invasive diagnostic biomarker.