The Metallome of Lung Cancer and its Potential Use as Biomarker

Abstract

Carcinogenesis is a very complex process in which metals have been found to be critically involved. In this sense, a disturbed redox status and metal dyshomeostasis take place during the onset and progression of cancer, and it is well-known that trace elements participate in the activation or inhibition of enzymatic reactions and metalloproteins, in which they usually participate as cofactors. Until now, the role of metals in cancer have been studied as an effect, establishing that cancer onset and progression affects the disturbance of the natural chemical form of the essential elements in the metabolism. However, it has also been studied as a cause, giving insights related to the high exposure of metals giving a place to the carcinogenic process. On the other hand, the chemical species of the metal or metallobiomolecule is very important, since it finally affects the biological activity or the toxicological potential of the element and their mobility across different biological compartments. Moreover, the importance of metal homeostasis and metals interactions in biology has also been demonstrated, and the ratios between some elements were found to be different in cancer patients; however, the interplay of elements is rarely reported. This review focuses on the critical role of metals in lung cancer, which is one of the most insidious forms of cancer, with special attention to the analytical approaches and pitfalls to extract metals and their species from tissues and biofluids, determining the ratios of metals, obtaining classification profiles, and finally defining the metallome of lung cancer.

Multielemental Analysis of Low-Volume Samples Reveals Cancer-Specific Profile in Serum and Sorted Immune Cells

“…Wach et al observed, among others, significantly increased levels of Ca, Cu, and Zn and decreased levels of Fe in serum of bladder cancer patients, and higher levels of serum P were found in lung cancer patients . Importantly, the serum Cu/Zn ratio has been shown to be a promising biomarker for lung cancer diagnosis, but other elemental ratios (e.g., V/Mn) might also be of diagnostic value for cancer . Overall, the existing literature is in line with our findings and points toward commonalities of specific elemental disturbances induced by the presence of a tumor.…”

Manganese systemic distribution is modulated in vivo during tumor progression and affects tumor cell migration and invasion in vitro

“…Trace elements, especially metals, are regulators of cellular homeostasis and present key roles on pathological processes, such as cancer 19 . They function as cofactors, electron donors and are central for bioelectrogenesis and electrophysiology.…”

Disease Ionomics: Understanding the Role of Ions in Complex Disease

“…Some other studies that only examined the levels of specific elements in different body fluids and tumor tissues also reported statistically significant differences from the distribution of certain elements, such as decreased Zn and elevated Cu concentrations in serum, and decreased Fe and Mn levels in urine and tumor tissues of LC patients [ 145 , 146 , 147 ]. Based on previously published metallomic/ionomic results, a recent review discussed the critical role of metals in LC, especially the importance of high exposure of metals, metal homeostasis and interactions, and metal speciation in cancer onset and progression, which indicates the potential use of such information in early diagnosis, prognosis, or therapy for LC [ 148 ].…”