Abstract

Background: The metabolic and hormonal axis that connects the dysfunction of adipose tissue with breast cancer has been identified as a very important pathobiological factor, Mostly in communities with high obesity rates like populations of southern Iraq. Adiponectin, which is an adipokine that has been found to inhibit cell growth and enhance insulin sensitivity, is negatively correlated with breast cancer risk However leptin, which is an inflammatory, angiogenic adipokine, helps the tumor grow and become more invasive. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), which is derived from fasting blood glucose and insulin levels, measures systemic insulin resistance, which is a potent breast carcinogenesis activator through the IGF-1 pathway. The current research focuses on the clinical biochemistry profile of serum adiponectin, leptin, and HOMA-IR in breast cancer patients and assesses their potential as independent biomarkers for breast cancer diagnosis and tumor stage stratification. Methods: We carried out a prospective case control study in Maysan Oncology Centre Amarah Iraq, where we collected 80 samples in total. The case group (n = 40) consisted of females with breast cancer that was confirmed by histopathology. These patients were at any stage of breast cancer (AJCC 8th stage) and were sampled before getting any treatment. Control group (n = 40) were healthy women matched individually by age and menopausal status. We performed all biomarker tests on blood samples taken from a fasting state. The amount of serum adiponectin and leptin was determined using a sandwich enzyme-linked immunosorbent assay (ELISA). Fasting insulin was determined by an electrochemiluminescence immunoassay (ECLIA). HOMA-IR was calculated as [fasting glucose (mmol/L) fasting insulin (IU/mL)] / 22.5. Results: Serum adiponectin levels were Quite a bit lower in breast cancer patients (6.34 2.18 vs. 14.82 3.64 g/mL; P < 0.001; Cohen's d = 2.84). In contrast, these patients had much higher leptin (28.74 7.63 vs. 12.46 3.82 ng/mL; P < 0.001; Cohen's d = 2.71) and HOMA-IR (4.26 1.18 vs. 1.94 0.54; P < 0.001; Cohen's d = 2.54) levels. Stage-wise changes of all the three markers showed a consistent worsening trend from AJCC Stages IIV. Besides being independent predictors of breast cancer, they were also the three factors considered by multivariate logistic regression. In ROC analysis, the respective AUC values were 0.948, 0.936, and 0.941. Not only were there very strong inter-marker correlations, significant associations with BMI, lipid profile, and tumour stage were also found. Conclusion: The adiponectin-leptin-HOMA-IR triad is a metabolically hormone-based biomarker panel for breast cancer that is mechanistically consistent, independently validated, and analytically accessible. Their significant stage-dependent changes and strong relationships with metabolic parameters point to adipose tissue dysfunction and insulin resistance as the biochemical promoters of breast cancer in the Maysan female population that can be measured through these biomarker panels.

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