Metabolomic investigation of urinary extracellular vesicles for early detection and screening of lung cancer

Abstract

Lung cancer is a prevalent cancer type worldwide that often remains asymptomatic in its early stages and is frequently diagnosed at an advanced stage with a poor prognosis due to the lack of effective diagnostic techniques and molecular biomarkers. However, emerging evidence suggests that extracellular vesicles (EVs) may promote lung cancer cell proliferation and metastasis, and modulate the anti-tumor immune response in lung cancer carcinogenesis, making them potential biomarkers for early cancer detection. To investigate the potential of urinary EVs for non-invasive detection and screening of patients at early stages, we studied metabolomic signatures of lung cancer. Specifically, we conducted metabolomic analysis of 102 EV samples and identified metabolome profiles of urinary EVs, including organic acids and derivatives, lipids and lipid-like molecules, organheterocyclic compounds, and benzenoids. Using machine learning with a random forest model, we screened for potential markers of lung cancer and identified a marker panel consisting of Kanzonol Z, Xanthosine, Nervonyl carnitine, and 3,4-Dihydroxybenzaldehyde, which exhibited a diagnostic potency of 96% for the testing cohort (AUC value). Importantly, this marker panel also demonstrated effective prediction for the validation set, with an AUC value of 84%, indicating the reliability of the marker screening process. Our findings suggest that the metabolomic analysis of urinary EVs provides a promising source of non-invasive markers for lung cancer diagnostics. We believe that the EV metabolic signatures could be used to develop clinical applications for the early detection and screening of lung cancer, potentially improving patient outcomes.

Non-targeted metabolomics analysis of indoleamine 2,3-dioxygenase inhibitor treatment in a mouse model of early-stage lung adenocarcinoma

“…A total of 348 metabolites were identified, with organic acids and derivatives (16.954%) and lipids and lipid-like molecules (15.517%) being the two major classes of metabolites in early-stage lung adenocarcinoma mice. This finding is consistent with previous research results ( 29 - 31 ), indicating that these two classes of metabolites play important roles in the development of early-stage lung adenocarcinoma.…”

Altered plasma metabolites and inflammatory networks in HIV-1 infected patients with different immunological responses after long-term antiretroviral therapy

“…Metabolomics has been widely applied to screening potential biomarkers and related disease mechanisms, which has been applied to liver disease ( 8 ), cardiovascular disease ( 9 ), cancer ( 10 ), and HIV infection ( 6 , 7 , 11 , 12 ). Several metabolomics studies of HIV infection suggest that ART could only partially recover the disturbed metabolic changes due to HIV infection ( 11 , 13 ).…”

Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma

“…Emerging research highlights the integral role of cancer metabolism not only in sustaining tumorigenesis and survival but also in modulating anti-tumor immune responses through metabolic byproducts and in uencing immune molecule expression [11,12]. Speci c pathways, such as cisplatin-mediated glucocorticoid receptor activation leading to resistance through the microtubule-associated serine/threonine kinase 1 via reprogramming MAPK pathway [13].…”