Connecting the changing metallomic spectrum and survival in sarcoma: a pilot study

<title>Abstract</title> Background The role of metals and trace elements in the progression of cancer can be both passive and active. While some metals have clearly emerged as carcinogens, the homeostasis of other trace elements only trails cancer evolution and therefore offers some potential prognostic values. At this stage, modern-standard datasets including a large number of elements are missing. The present analysis established a first metallomic spectrum by relating the blood concentration of metals and trace elements in patients with sarcoma with survival data. Methods Patients with sarcoma and controls were retrospectively selected from the International Sarcoma Kindred Study database. Blood samples were prospectively collected at the Leon Bérard Cancer Center from February 2012 to July 2019. Stable specimens and copper isotopes (65Cu/63Cu) were analyzed using Triple Quadrupole ICP-MS and the MC-ICP-MS Nu Plasma HR 500. Wilcoxon rank sum test, log-rank test, and multivariate Cox regression models were used for statistics. Results In total, 151 patients and 59 healthy controls were included. At the time of blood sample collection, 62% of patients had locally advanced or metastatic disease, and 49% were undergoing chemotherapy. The median overall survival (OS) was 16.6 months. Copper (Cu), copper/zinc (Cu/Zn) and potassium /rubidium (K/Rb) ratio were significantly higher in patients compared to controls, whereas δ65Cu, selenium (Se), sulfur (S), Rb, K, phosphorus (P), iron (Fe) and Se / S ratio were significantly lower. Cu, Cu / Zn and K / Rb were also significantly higher in advanced compared to early stage disease. Of note, whereas S and Se were significantly correlated in patients, no correlation was observed in controls. Importantly, levels of K, Rb, Se, Fe, P, Si, S, δ65Cu, Cu, S / Se and Cu/Zn ratio were independently associated with OS. Conclusions These results depict the metallomic spectrum in sarcoma and highlight substantial variation associated with survival, some of them paving the way for future anti-cancer therapy development