Patterns of Carbon-Bound Exogenous Compounds in Patients with Lung Cancer and Association with Disease Pathophysiology

Abstract

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.

MALDI Mass Spectrometry Imaging—Prognostic Pathways and Metabolites for Renal Cell Carcinomas

“…In order to determine the prognostic power for each metabolite, the individual patient metabolite abundances were used to split the cohort into good and poor survivor groups by the application of intensity cutoffs, which were optimized to the clinical endpoint. Cutoff-optimized survival analyses were performed as previously described [ 23 , 24 ] using a Kaplan–Meier Fitter and log-rank test. Cutoff-optimized in this context means that the threshold for low and high abundance of a compound was chosen such that the p -value in the resulting Kaplan–Meier curve is minimal.…”

Spatial metabolomics for evaluating response to neoadjuvant therapy in non‐small cell lung cancer patients

“…The entire workflow is applied to the same tissue section, allowing for the automatic integration of morphological and spatial metabolomics data for thousands of molecules. We established this method and have successfully applied it in previous works [27,[44][45][46]. Supplementary Figure S1 displays representative immunofluorescence sections used during this process.…”

Patterns of Carbon-Bound Exogenous Compounds Impact Disease Pathophysiology in Lung Cancer Subtypes in Different Ways

“…12 Our previous study demonstrated that carbon-bound PAHs, tobacco-specific nitrosamines, aromatic amines, and organohalogens are strongly associated with patient outcomes, tumor development, and the tumor microenvironment in lung squamous cell carcinoma (LUSC). 13 However, the roles of these exogenous compounds in lung adenocarcinoma (LUAD) remain unclear. LUAD is the most common lung cancer type, accounting for 30% of all lung cancer cases and approximately 40% of all nonsmall cell lung cancer (NSCLC) occurrences.…”

“…Zhang et al found that the polycyclic aromatic hydrocarbon (PAH) accumulation in pulmonary carbon particles increases with age, which could potentially increase the risk of lung cancer development . Our previous study demonstrated that carbon-bound PAHs, tobacco-specific nitrosamines, aromatic amines, and organohalogens are strongly associated with patient outcomes, tumor development, and the tumor microenvironment in lung squamous cell carcinoma (LUSC) . However, the roles of these exogenous compounds in lung adenocarcinoma (LUAD) remain unclear.…”