Cu and Zn isotope ratio variations in plasma for survival prediction in hematological malignancy cases

We have examined potential changes in the isotopic compositions of Fe, Cu and Zn (using multi-collector inductively coupled plasma-mass spectrometry) and the corresponding concentrations (using inductively coupled plasma-atomic emission spectrometry) in plasma from hematological malignancy (HM) patients and assessed their prognostic capability. Together with clinical laboratory test values, data were examined in view of a 5-years survival prediction. Plasma Cu and Zn isotope ratios and their concentrations were significantly different in HM patients compared to matched controls (P < 0.05). Both δ⁶⁵Cu and δ⁶⁶Zn values showed significant mortality hazard ratios (HRs) in HM. The group of patients with decreased δ⁶⁵Cu and increased δ⁶⁶Zn values showed significantly poorer survival from the early phase (HR 3.9; P = 0.001), forming a unique cohort not identified based on laboratory test values. Well-known prognostic factors for HM, such as the creatinine level, and anemia-related values were highly correlated with the δ⁶⁶Zn value (P < 0.05). Time-dependent ROC curves based on the δ⁶⁵Cu or δ⁶⁶Zn value were similar to that based on the creatinine concentration (a well-known prognostic factor in HM), indicating that δ⁶⁵Cu or δ⁶⁶Zn values are useful for prognosis of HM. Variations in stable isotope ratios of essential mineral elements have thus been shown to reflect alterations in their homeostasis due to physiological changes in malignancies with higher sensitivity than concentrations do.