Asymptomatic anthracosis is the accumulation of black carbon particles in adult human lungs. It is a common occurrence, but the pathophysiologic significance of anthracosis is debatable. Using in situ high mass resolution matrix-assisted laser desorption/ionization (MALDI) fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging analysis, we discovered noxious carbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAH), tobacco-specific nitrosamines, or aromatic amines, in a series of 330 patients with lung cancer in highly variable and unique patterns. The characteristic nature of carbon-bound exogenous compounds had a strong association with patient outcome, tumor progression, the tumor immune microenvironment, programmed death-ligand 1 (PD-L1) expression, and DNA damage. Spatial correlation network analyses revealed substantial differences in the metabolome of tumor cells compared with tumor stroma depending on carbon-bound exogenous compounds. Overall, the bioactive pool of exogenous compounds is associated with several changes in lung cancer pathophysiology and correlates with patient outcome. Given the high prevalence of anthracosis in the lungs of adult humans, future work should investigate the role of carbon-bound exogenous compounds in lung carcinogenesis and lung cancer therapy. Significance: This study identifies a bioactive pool of carbon-bound exogenous compounds in patient tissues associated with several tumor biological features, contributing to an improved understanding of drivers of lung cancer pathophysiology.

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肺癌患者碳结合外源性化合物的模式及其与疾病病理生理学的关系

无症状炭疽病是黑碳颗粒在成人肺部的积聚。这是一种常见的现象，但炭疽病的病理生理意义是有争议的。使用原位高质量分辨率基质辅助激光解吸/电离 (MALDI) 傅里叶变换离子回旋共振 (FT-ICR) 质谱成像分析，我们发现了有毒的碳结合外源化合物，例如多环芳烃 (PAH)，烟草特有的亚硝胺或芳香胺，在一系列 330 名肺癌患者中以高度可变和独特的模式出现。碳结合外源化合物的特征与患者预后、肿瘤进展、肿瘤免疫微环境、程序性死亡配体 1 (PD-L1) 表达和 DNA 损伤密切相关。空间相关网络分析显示，与肿瘤基质相比，肿瘤细胞的代谢组存在显着差异，这取决于碳结合的外源化合物。总体而言，外源性化合物的生物活性库与肺癌病理生理学的一些变化相关，并与患者预后相关。鉴于成人肺部炭疽病的高发病率，未来的工作应该研究碳结合的外源性化合物在肺癌发生和肺癌治疗中的作用。意义：本研究确定了患者组织中与多种肿瘤生物学特征相关的碳结合外源化合物的生物活性池，有助于加深对肺癌病理生理学驱动因素的理解。