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

SIMPLE SUMMARY: Considerable progress in the treatment of non–small cell lung cancer (NSCLC) has been made possible by large-scale technologies that scan the gene expression in tumor cells. While gene expression is informative, it is the changes to cellular metabolism that directly affect the initiation and the progression of the disease. Altered metabolic processes in cancer include how the tumor cells handle fat, proteins, and sugar, produce energy, divide (grow), or migrate. We have used nuclear magnetic resonance and mass spectrometry to survey and document the metabolic changes in blood and urine samples collected from NSCLC patients before and after their lung tumors were surgically removed. We found several molecular compounds that changed in abundance in the blood or urine after surgery, many of which are related to cancer cell metabolism. Further documentation of these changes in large patient populations will lead to non-invasive ways to screen, diagnose, or monitor disease progression in lung cancer patients. 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.