A critical review on the relevance, essentiality, and analytical techniques of trace elements in human cancer

Trace elements (TEs) are indispensable nutritional elements, playing a pivotal role in maintaining human health and serving as essential cofactors for numerous enzymes that facilitate crucial biological processes. The dysregulation (excess or deficiency) of TEs can affect the proper functioning of various organs and lead to diseases like cancer. However, the current research findings remain contentious, and the association between TE variations and cancer remains elusive. This article reviews the recent advances in the quantitative detection of TEs in tumor research to fully understand the important role of TEs in disease diagnosis and prognosis. The changes in the levels of various elements (such as Cu, Zn, Fe, Se, Ca, etc.) are analyzed and summarized from five systems of the human body, including the digestive system, urinary system, reproductive system, endocrine system, and respiratory system. By analyzing the relevant findings in diverse biological samples, we systematically investigate the disruption of TEs homeostasis in cancer patients, thereby underscoring the potential of TEs as cancer biomarkers. We also present novel analytical techniques such as isotope ratio determination and bioimaging, along with advanced auxiliary tools like machine learning, for the detection of TEs in disease research. This review aims to provide a comprehensive overview of TEs variations in the main cancer types of different systems, which addresses the knowledge gap in TEs on human health, and provides proposals for future research.