Elevated Serum Nidogen-2 and Dysregulated Physiological Markers in Iraqi Women with Breast Cancer: A Case-Control Study with In Silico Validation

Abstract

Background: Breast cancer is one of the major health concerns worldwide, which needs biomarkers for proper diagnosis. Serum Nidogen-2 (NID2), along with other physiological and inflammatory biomarkers, has been proposed as a non-invasive method for breast cancer diagnosis. The current study was conducted to assess the diagnostic value of serum Nidogen-2 and physiological parameters in Iraqi breast cancer patients. Materials and Methods: This is a case-control study done in Ramadi, Iraq, where 60 women were divided into two groups: 30 women suffering from breast cancer and 30 control women. This study focused on serum Nidogen-2 (NID2), Estrogen, C reactive protein (CRP), kidney function markers (urea, uric acid, and potassium), and anthropometric measurements. The Receiver Operating Characteristic (ROC) curve test was carried out to determine their diagnostic efficacy. Furthermore, NID2 mRNA expression data in breast tumors versus breast normal tissues were determined using the TCGA BRCA dataset. Results: Significant differences were discovered in serum levels of Nidogen-2, as breast cancer patients had increased serum levels (154.17 ± 25.42 pg/ml) compared to the healthy controls (108.85 ± 20.10 pg/ml, p<0.0001). Estrogen levels were also significantly decreased in breast cancer patients (48.34 ± 11.62 pg/ml) compared to healthy controls (99.83 ±11.59 pg/ml, p < 0.0001). Other markers of renal function and inflammation, Urea, Uric acid, and Potassium (K+), were also significantly higher in breast cancer patients compared to healthy controls. Excellent diagnostic performance for breast cancer was determined by Receiver Operating Characteristic (ROC) curve analysis for Estrogen (AUC = 1.000), Nidogen-2 (AUC = 0.938), and CRP (AUC 0.963). In silico validation for NID2 mRNA was completed using the Cancer Genome Atlas (TCGA) Breast Cancer (BRCA) dataset, where NID2 gene expression was ↑ in breast cancer tissue compared to normal breast tissue (p=0.00012), demonstrating breast cancer identified by the use of Nidogen-2, Estrogen, and CRP. Conclusion: Serum Nidogen-2, Estrogen, and CRP demonstrate high diagnostic capacity for breast cancer in Iraqi women, backed by bioinformatic validation of NID2 tissue expression, suggesting their efficacy as valuable diagnostic biomarkers.