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.