Trace metal signatures in non-small cell lung cancer: A pilot study of patients attended at Mount Sinai Hospital in New York City

Abstract Background: Non-small cell lung cancer (NSCLC) is increasing worldwide, yet the environmental and mechanistic contributors driving tumor development and aggressiveness remain poorly defined. Metals and trace elements-ubiquitously present in air pollution-can induce oxidative stress, potentially generating DNA damage that remodels tumor metabolism and promotes malignancy. We evaluated the feasibility of integrating metal profiling in malignant and normal NSCLC tissues and identified preliminary correlations between trace elements and malignancy status. Methods: Ten OCT-embedded lung adenocarcinoma cases from an urban cohort of patients attended and biobanked at the Mount Sinai Biorepository underwent laser-capture microdissection to isolate paired tumor and adjacent normal tissue. Twenty-three metals and trace elements were quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) following nitric acid digestion. Logistic regression models (unadjusted due to sample size) were used to evaluate associations with tumor status. Linear regressions were used for tumor size. Results: Tumor tissue demonstrated distinct metal signatures. Magnesium (Mg) and selenium (Se) were significantly enriched in tumors (Mg: Odds ratio [OR]=4.79, 95% Confidence Interval [95% CI]: 1.10-20.82; Se: OR=18.93, 95% CI: 1.48-242.44), while nickel (Ni) and zinc (Zn) showed positive trends toward tumor accumulation. Iron (Fe) was markedly higher in normal tissue. Additional analyses revealed inverse associations between tumor size and chromium (Cr; beta = -1.34, 95%CI: -2.41, -0.27, p = 0.02*), manganese (Mn; beta = -1.06, 95%CI: -2.32, 0.199, p = 0.09*), and cesium (Cs; beta = -1.10, 95%CI: -2.16, -0.04, p = 0.04*). Conclusions: Preliminary data demonstrate the feasibility of multiple metal and trace element quantification in NSCLC tissues, revealing potential specific perturbations associated with tumor presence and aggressiveness. The observed enrichment of Mg, Se, and Ni in tumors supports a potential mechanistic link between metal exposure, trace element imbalance, and malignant phenotypes, which may contribute to NSCLC tumorigenesis in urban populations. Ongoing analyses will integrate mitochondrial mtDNA heteroplasmy variants from these NSCLC samples to elucidate metal-mitochondrial interactions driving tumor biology. Keywords: "NSCLC," "Trace Metals," "Environmental Carcinogenesis," "Tumor Microenvironment."