Efficient Cancer Biomarker Screening and Multicancer Detection Enabled by a Multidimensional Serum Proteomic Strategy

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