Serum and Whole Blood Cu and Zn Status in Predicting Mortality in Lung Cancer Patients

Abstract

Alterations in circulating Cu and Zn are negative predictors of survival in neoplastic patients and are known during lung cancer. However, no data on predicting mortality of lung cancer patients based on the level of these elements in the blood have been presented to date. The aims of this prospective cohort study were as follows: (i) To evaluate the disturbances in serum and whole blood Cu and Zn, (ii) to assess the relationships between serum and whole blood Cu and Zn status and clinical, sociodemographic, and nutritional data, and (iii) to investigate the association of Cu and Zn status with all-cause mortality in lung cancer. Naïve-treatment lung cancer patients (n = 167) were characterized in terms of sociodemographic, clinical, and anthropometric data and dietary intake and compared with sex-matched control subjects (n = 48). Whole blood and serum Cu and Zn status was determined by atomic absorption spectrometry. Cox proportional hazards models adjusted for multiple confounders/mediators were used to estimate the association between all-cause death and Cu and Zn status. Sex, cardiovascular disease, chronic obstructive pulmonary disease, clinical stage, and hemoglobin, platelet, and glucose concentrations significantly differentiated Cu and Zn status. All-cause mortality in lung cancer patients was positively associated with serum Cu levels, Cu:Zn ratio, and whole blood Zn levels. However, an advanced clinical stage of disease was the strongest predictor of all-cause mortality. Circulatory status of Cu and Zn might be included in routine clinical characteristics of patients with lung cancer patients as additional prognostic variables, but only after further more detail studies.

Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance

“…Similar to Cu levels, the ratio of serum Cu/Zn levels was also significantly higher in cancer patients compared to healthy controls, which typically resulted from the increase of Cu levels with simultaneous decrease of Zn levels. Recently, several studies aimed to determine whether circulating Cu levels in serum and full blood, and the ratio of Cu/Zn levels can serve as predictors of the patients’ mortality [ 32 , 33 , 34 , 35 ]. It was demonstrated that higher serum Cu levels, as well as Cu/Zn ratio, were associated with increased all-cause mortality in lung cancer patients [ 32 ].…”

“…Recently, several studies aimed to determine whether circulating Cu levels in serum and full blood, and the ratio of Cu/Zn levels can serve as predictors of the patients’ mortality [ 32 , 33 , 34 , 35 ]. It was demonstrated that higher serum Cu levels, as well as Cu/Zn ratio, were associated with increased all-cause mortality in lung cancer patients [ 32 ]. This might be associated with the increase of Cu levels and Cu/Zn ratio at advanced stages of the disease, as well as during metastatic progression, thus resulting in lowered survivability [ 32 , 33 , 34 , 35 ].…”

“…It was demonstrated that higher serum Cu levels, as well as Cu/Zn ratio, were associated with increased all-cause mortality in lung cancer patients [ 32 ]. This might be associated with the increase of Cu levels and Cu/Zn ratio at advanced stages of the disease, as well as during metastatic progression, thus resulting in lowered survivability [ 32 , 33 , 34 , 35 ]. It was suggested that elevation of serum/blood Cu levels might be a consequence of Cu ions release from necrotic tumor tissues [ 36 ] or a result of an inflammatory condition [ 37 , 38 ].…”

Selenium, Copper, Zinc Concentrations and Cu/Zn, Cu/Se Molar Ratios in the Serum of Patients with Acute Ischemic Stroke in Northeastern Poland—A New Insight into Stroke Pathophysiology

“…It is thought that an elevated fraction of free cooper in serum may be harmful due to its significant oxidation–reduction potential through the generation of reactive oxygen species in Fenton and Haber–Weiss type reactions [ 21 ]. They are essential to the operating of the immune system and proper functioning of a variety of physiological and biochemical processes [ 22 , 23 ]. Apart from being a cofactor for numerous enzymes, they play the key role in the development and functioning of the central nervous system [ 24 , 25 , 26 ].…”

The molecular and cellular basis of copper dysregulation and its relationship with human pathologies

“…567 Changes in systemic levels of transition metals occur during carcinogenesis and vary according to the type of cancer, metal ion, and other biological factors. [568][569][570][571][572][573][574][575] Proliferating cancer cells have a higher demand for Cu than normal cells, 576 so limiting Cu availability during carcinogenesis might be a way to slow cancer progression. 577 Conversely, high levels of Cu can inhibit cell proliferation and tumor growth.…”