Lipidomes of lung cancer and tumour-free lung tissues reveal distinct molecular signatures for cancer differentiation, age, inflammation, and pulmonary emphysema

Abstract

Little is known about the human lung lipidome, its variability in different physiological states, its alterations during carcinogenesis and the development of pulmonary emphysema. We investigated how health status might be mirrored in the lung lipidome. Tissues were sampled for both lipidomic and histological analysis. Using a screening approach, we characterised lipidomes of lung cancer tissues and corresponding tumour-free alveolar tissues. We quantified 311 lipids from 11 classes in 43 tissue samples from 26 patients. Tumour tissues exhibited elevated levels of triacylglycerols and cholesteryl esters, as well as a significantly lower abundance of phosphatidylglycerols, which are typical lung surfactant components. Adenocarcinomas and squamous cell carcinomas were distinguished with high specificity based on lipid panels. Lipidomes of tumour biopsy samples showed clear changes depending on their histology and, in particular, their proportion of active tumour cells and stroma. Partial least squares regression showed correlations between lipid profiles of tumour-free alveolar tissues and the degree of emphysema, inflammation status, and the age of patients. Unsaturated long-chain phosphatidylserines and phosphatidylinositols showed a positive correlation with a worsened emphysema status and ageing. This work provides a resource for the human lung lipidome and a systematic data analysis strategy to link clinical characteristics and histology.

Metabolic characteristics of large and small extracellular vesicles from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy

“…EVs have been identified as important metabolite cargos for the cancer cell metabolism [ 46 , 62 ]. TGs are main energy storage, interestingly elevated levels of TGs have been found in the tumour tissues of lung cancer [ 63 ]. Fatty acids can be utilized to supply energy by β-oxidation, which can be mediated by acyl-CoA aynthetase long-chain 3 and accelerate the lung tumorigenesis [ 64 ].…”

ROS from Physical Plasmas: Redox Chemistry for Biomedical Therapy

“…This suggests a concomitance of both processes and emphasizes that lipid oxidation and/or chain cleavage are key factors determining membrane fluidity and polarity and ultimately membrane penetration. Of note, the membrane lipid composition of normal and cancer cells differ in the reflection of their metabolic state, contributing to a certain graduation of the impact of plasma or other prooxidant physical treatment regimens [227, 228].…”

Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways

“…The high concentrations of mitochondrial ROS in the presence of lipids that can act as electron acceptors suggests that the mitochondria could be an important site of lipid peroxidation. In addition, mitochondria-derived ROS can diffuse into the cytosol and attack extra-mitochondrial lipids, as well as other molecules and, consequently, several VOCs could be released due to peroxidation of cancer-specific lipid species and/or due to ROS-mediated oxidation [49][50][51].…”