Serum metabolomics profiling reveals metabolic alterations prior to the diagnosis with non-small cell lung cancer among Chinese community residents: a prospective nested case-control study

Background: The present high mortality of lung cancer in China stems mainly from the lack of feasible, noninvasive early disease detection biomarkers. Serum metabolomics profiling prior to diagnosis to reveal metabolic alterations could expedite the disease detection process and suggest patients harboring disease. We identified differential expressed metabolites and their involved biological processes of non-small cell lung cancer (NSCLC) among the Chinese community residents. Methods Using a nested case-control design, we applied ultra-high-performance liquid chromatography / mass spectrometry (LC-MS)-based serum metabolomics to reveal metabolomic alterations and indicate the NSCLC presence using serum samples collected prior to their disease diagnoses. Studied serum samples were collected from 41 patients before NSCLC diagnosis (within 3.0 y) and 38 matched cancer-free controls from the prospective Shanghai Suburban Adult Cohort recruited from April 2016 to October 2017 at Songjiang District, Shanghai, China. Results NSCLC patients presented markedly cellular metabolism alterations in serum samples collected prior to their disease diagnoses compared with cancer-free controls. In total, we identified 18 significantly expressed metabolites whose relative abundance showed either an upward or a downward trend, with most of them where lipid and lipid-like molecules, organic acids, and nitrogen compounds. Choline metabolism in cancer exhibits a markedly metabolic disturbance in NSCLC patients, followed by sphingolipid and glycerophospholipid metabolism. Our data point to the aforementioned metabolisms and related metabolites as potential vital targets for cancer interventions and could improve the early diagnosis of NSCLC patients. Our results demonstrate the potential feasibility of LC-MS-based serum metabolomics to predict the presence of NSCLC combined with characteristics including smoking habits and the exposure history of second-hand smoking. With further validation, metabolomic techniques could be used as an effective but less-invasive tool to supplement the screening programs of NSCLC in the Chinese population. Interpretation: Choline metabolism in cancer, sphingolipid, and glycerophospholipid metabolism emerge as the significant metabolic disturbance of NSCLC. Metabolites involved in these biological processes may be the distinctive features associated with NSCLC prior to diagnosis.