Efficient Cancer\nBiomarker Screening and Multicancer\nDetection Enabled by a Multidimensional Serum Proteomic Strategy

Biomarker discovery and application are paramount for\nthe early\ndiagnosis, treatment, and prognosis assessment of diseases. Novel\nproteomic strategies have been developed for high-efficiency biomarker\nscreening. However, evaluating various strategies and applying them\nfor the in-depth mining of biomarkers from blood need to be elucidated.\nHerein, we systematically evaluated the technical characteristics\nof three representative biomarker discovery strategies, including\nthe most popular DIA proteomics, and two promising strategies targeting\nthe cancer-secreted proteome or extracellular vesicle proteome, and\nintegrated them into one multidimensional serum proteomic strategy.\nThe results showed that the three strategies each have unique characteristics\nin terms of sensitivity, reproducibility, and protein coverage and\nare highly complementary in biomarker discovery. The integrated multidimensional\nserum proteomic strategy achieves deep and comprehensive coverage\nof the serum proteome, discovers more cancer markers, and helps achieve\na more accurate multicancer (breast, lung, stomach, liver, and colorectum)\ndiagnosis with 87.5% localization accuracy.