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Abstract
As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.
As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. Here, the authors report a machine learning model using mass spectrometry-based liquid biopsy data for pan-cancer screening and classification.
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1 National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China (GRID:grid.13291.38) (ISNI:0000 0001 0807 1581)
2 Department of Endocrinology and Metabolism, Fudan Institute of Metabolic Diseases, Zhongshan Hospital, Fudan University, Shanghai, China (GRID:grid.413087.9) (ISNI:0000 0004 1755 3939)
3 State Key Laboratory of Information Engineering in Surveying, Mapping and Remote Sensing, Wuhan University, Wuhan, China (GRID:grid.49470.3e) (ISNI:0000 0001 2331 6153)
4 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Department of Liver Surgery and Transplantation, Shanghai, China (GRID:grid.413087.9) (ISNI:0000 0004 1755 3939)
5 Zhongshan Hospital, Fudan University, Department of Oncology, Shanghai, China (GRID:grid.413087.9) (ISNI:0000 0004 1755 3939)
6 Zhongshan Hospital, Fudan University, Department of General Surgery, Shanghai, China (GRID:grid.413087.9) (ISNI:0000 0004 1755 3939)
7 Zhongshan Hospital, Fudan University, Department of Thoracic Surgery, Shanghai, China (GRID:grid.413087.9) (ISNI:0000 0004 1755 3939)
8 School of Pharmaceutical Sciences, Tsinghua University, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178)
9 National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Department of Orthopaedic Surgery, Chengdu, China (GRID:grid.412901.f) (ISNI:0000 0004 1770 1022)
10 School of Software, Tsinghua University, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178)
11 CAS Key Laboratory of Nutrition, Metabolism and Food safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China (GRID:grid.507675.6)
12 the First Affiliated Hospital, Institute for Liver Diseases of Anhui Medical University, Department of Oncology, Hefei, China (GRID:grid.186775.a) (ISNI:0000 0000 9490 772X)
13 University of California, Department of Chemistry and Biochemistry, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); California NanoSystems Institute, University of California, Los Angeles, USA (GRID:grid.509979.b) (ISNI:0000 0004 7666 6191)