Metabolic Changes in Early-Stage Non–Small Cell Lung Cancer Patients after Surgical Resection

Abstract

Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.

Metabolic Alterations in Sputum and Exhaled Breath Condensate of Early Stage Non-Small Cell Lung Cancer Patients After Surgical Resection: A Pilot Study

“…Although this pilot study features a relatively small sample size, the results likely represent the biological and metabolic state of the lower respiratory tract of early-stage NSCLC patients before and after SR of the cancerous tumors. Metabolic alterations were most pronounced with regards to lipid metabolism as compared to other classes of metabolites, which is consistent with previous publications (16,31). However, there was no specific pattern of dysregulation; the magnitude of up-and downregulated lipid metabolites was similar (Figure 3 and Table 4).…”

“…Three hundred ml of sputum was extracted and transferred into an Eppendorf tube and 300 ml of 2 M NaCl solution (pH = 7.4) and 20 ml of TSP (0.75%) were added. NMR data were obtained utilizing the Bruker software TopSpin version 3.5 pl 7, on a Bruker Ascend 600 spectrometer at 600.27 and 150.938 MHz for proton and carbon nuclei, respectively, using the specific parameters previously described (16). In summary, each sample was subject to two separate scans at a probe temperature of 298 K. A few randomly selected samples were run using the correlated spectroscopy (COSY) for additional analysis.…”

Defining the landscape of metabolic dysregulations in cancer metastasis

“…Our study is in agreement with his observation as we found elevated levels of glycerophospholipids and sphingomyelins in HMP cell lines and also suggesting enhanced lipid synthesis in cells with HMP. Changes in various lipid levels were found in subjects with non–small cell lung cancer (NSCLC) after tumor resection, further suggested role of lipid metabolism in tumor progression [ 68 ] and pointing it as a treatment target [ 69 ].Additionally, we observed an increase in the catabolic pathway of BCAA in HMP cell lines manifested by the accumulation of their products of catabolism in both cell and growth media. The products of leucine catabolism, namely 2-hydroxy-3-methylvalerateand alpha-hydroxyisocaproate, displayed the greatest accumulation in HMP cell lines in comparison with LMP cell lines.…”

Monitoring non-small cell lung cancer progression and treatment response through hyaluronic acid in sputum

“…The genomic, proteomic, and transcriptomic profiling of lung cancers is now being complemented by the study of the biochemical properties of endogenous metabolites produced by malignant cells ( 4 ). In this regard, a major polysaccharide component of the extracellular matrix, hyaluronan (HA), has attracted the attention of researchers because of its biochemical properties and its ability to control cell proliferation and migration through interactions with cell-surface receptors and binding molecules ( 5 ).…”