Zinc stable isotopes in urine as diagnostic for cancer of secretory organs

Breast, prostate, and pancreatic cancers alter the zinc (Zn) metabolism. Combined analyses of urinary Zn concentrations [Zn] and Zn stable isotope compositions (delta Zn-66) may provide a non-invasive approach for tracing malignancy-induced Zn dyshomeostasis. In this study, we measured [Zn] and delta Zn-66 in urine from prostate (n = 22), breast (n = 16), and from women with benign breast disease (n = 14) and compared those with age-matched healthy controls (22-49 years or 50+ years) and published data for pancreatic cancer (n = 17). Our results show that cancer-induced changes are reflected in higher urinary [Zn] and lower urinary delta Zn-66 for pancreatic and prostate cancer and benign breast disease when compared with healthy controls. For prostate cancer, the progression of low [Zn] and high delta Zn-66 for patients of low-risk disease toward high [Zn] and low delta Zn-66 for the higher risk patients demonstrates that [Zn] and delta Zn-66 in urine could serve as a reliable prognostic tool. Urinary excretion of isotopically light Zn by patients with prostatic and pancreatic cancer is probably the result of increased reactive oxygen species in cancerous cells, which limits the scavenging of hydroxyl radicals and thus facilitates the oxidation of metalloproteins with sulfur-rich ligands. Urine from breast cancer patients shows undistinguishable delta Zn-66 to healthy controls, implying that the expression of metalloproteins with sulfur-rich ligands is stronger in breast cancer tissues. In conclusion, urinary delta Zn-66 may provide a non-invasive diagnostic tool for pancreatic cancer and support disease prognosis for prostate cancer. These findings should translate to comprehensive transverse and longitudinal cohort studies in future.

Automated summary

Breast, prostate, and pancreatic cancers alter zinc metabolism, and analysis of urinary zinc concentrations and zinc stable isotope compositions can be used as a non-invasive method to trace malignancy-induced zinc imbalance. Patients with prostate and pancreatic cancer, as well as benign breast disease, show higher urinary zinc concentrations and lower delta Zn-66 compared to healthy controls, while breast cancer patients show undistinguishable zinc stable isotope compositions from the controls.