PO.MCB09.05 · 分子与细胞生物学
非小细胞肺癌中的微量金属特征：一项针对纽约市西奈山医院就诊患者的初步研究
Trace metal signatures in non-small cell lung cancer: A pilot study of patients attended at Mount Sinai Hospital in New York City
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：非小细胞肺癌（NSCLC）在全球范围内呈上升趋势，然而驱动肿瘤发生和侵袭性的环境及机制性因素仍未明确界定。金属和微量元素——在空气污染中普遍存在——可诱导氧化应激，可能产生DNA损伤，从而重塑肿瘤代谢并促进恶性转化。我们评估了在恶性和正常NSCLC组织中整合金属谱分析的可行性，并鉴定了微量元素与恶性状态之间的初步相关性。
方法：来自城市队列、在西奈山生物样本库就诊并生物储存的10例OCT包埋肺腺癌病例，接受激光捕获显微切割以分离配对的肿瘤和相邻正常组织。经硝酸消化后，采用电感耦合等离子体质谱（ICP-MS）对23种金属和微量元素进行定量。使用逻辑回归模型（因样本量原因未经校正）评估与肿瘤状态的关联。使用线性回归分析肿瘤大小。
结果：肿瘤组织表现出独特的金属特征。镁（Mg）和硒（Se）在肿瘤中显著富集（Mg：比值比[OR]=4.79，95%置信区间[95% CI]：1.10-20.82；Se：OR=18.93，95% CI：1.48-242.44），而镍（Ni）和锌（Zn）显示出向肿瘤蓄积的正向趋势。铁（Fe）在正常组织中明显更高。额外分析揭示肿瘤大小与铬（Cr；beta = -1.34，95% CI：-2.41，-0.27，p = 0.02*）、锰（Mn；beta = -1.06，95% CI：-2.32，0.199，p = 0.09*）和铯（Cs；beta = -1.10，95% CI：-2.16，-0.04，p = 0.04*）之间存在负相关。
结论：初步数据证明了在NSCLC组织中进行多种金属和微量元素定量的可行性，揭示了与肿瘤存在和侵袭性相关的潜在特异性扰动。观察到的Mg、Se和Ni在肿瘤中的富集，支持金属暴露、微量元素失衡与恶性表型之间存在潜在机制联系，这可能促成城市人群中的NSCLC肿瘤发生。正在进行的分析将整合来自这些NSCLC样本的线粒体mtDNA异质性变异，以阐明驱动肿瘤生物学的金属-线粒体相互作用。
关键词："NSCLC"、"微量金属"、"环境致癌"、"肿瘤微环境"。
查看英文原文 English abstract
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."
利益披露 Disclosure
D. Prada, None..
J. landero, None..
J. Abdul Ghafar, None.