Cancer Serum Atlas-Supported Precise Pan-Targeted Proteomics Enable Multicancer Detection

The wide dynamic range of serum proteome restrained discovery of clinically interested proteins in large cohort studies. Herein, we presented a high-sensitivity, high-throughput, and precise pan-targeted serum proteomic strategy for highly efficient cancer serum proteomic research and biomarker discovery. We constructed a resource of over 2000 cancer-secreted proteins, and the standard MS assays and spectra of at least one synthetic unique peptide per protein were acquired and documented (Cancer Serum Atlas, www.cancerserumatlas.com). Then, the standard peptide-anchored parallel reaction monitoring (SPA-PRM) method was developed with support of the Cancer Serum Atlas, achieving precise quantification of cancer-secreted proteins with high throughput and sensitivity. We directly quantified 325 cancer-related serum proteins in 288 serums of four cancer types (liver, stomach, lung, breast) and controls with the pan-targeted strategy and discovered considerable potential biomarker benefits for early detection of cancer. Finally, a proteomic-based multicancer detection model was built, demonstrating high sensitivity (87.2%) and specificity (100%), with 73.8% localization accuracy for an independent test set. In conclusion, the Cancer Serum Atlas provides a wide range of potential biomarkers that serve as targets and standard assays for systematic and highly efficient serological studies of cancer. The Cancer Serum Atlas-supported pan-targeted proteomic strategy enables highly efficient biomarker discovery and multicancer detection and thus can be a powerful tool for liquid biopsy.

Automated summary

A high-sensitivity, high-throughput, and precise pan-targeted serum proteomic strategy was developed for efficient cancer serum proteomic research and biomarker discovery. The strategy utilized the Cancer Serum Atlas to acquire standard MS assays and spectra of cancer-secreted proteins and employed the peptide-anchored parallel reaction monitoring (SPA-PRM) method for precise quantification. With this strategy, 325 cancer-related serum proteins were quantified in 288 serums, leading to the discovery of potential biomarkers for early cancer detection. A proteomic-based multicancer detection model was built, showing high sensitivity, specificity, and localization accuracy. The Cancer Serum Atlas provides a wide range of potential biomarkers and the pan-targeted proteomic strategy enables efficient biomarker discovery and multicancer detection.