Copper isotope fractionation and copper-to-zinc ratios reveal altered metal homeostasis in prostate cancer.

Trace metal homeostasis is increasingly recognized as a reflection of cellular metabolism and redox balance. This study applies high-precision copper isotope and elemental ratio analysis to human serum to investigate how prostate cancer alters systemic metal regulation. Using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) adapted from geochemical applications, we quantified copper isotope fractionation and Cu/Zn ratios across disease stages. Patients with localized or newly metastatic prostate cancer exhibited isotopically heavier serum copper compared to healthy controls, while advanced, castration-resistant disease showed higher copper concentrations, lower zinc levels, and elevated Cu/Zn ratios. Together, these findings suggest that prostate cancer-associated alterations in copper and zinc homeostasis may reflect modulation by sex steroid-dependent physiological states. They also demonstrate the sensitivity of MC-ICP-MS in detecting subtle isotopic shifts in biological samples and establish its value as a tool for characterizing metabolic and redox alterations in prostate cancer.