Novel proteomics-based plasma test for early detection of multiple cancers in the general population

Abstract

Objective Early detection of cancer is crucial for reducing the global burden of cancer, but effective screening tests for many cancers do not exist. This study aimed to develop a novel proteome-based multi-cancer screening test that can detect early-stage cancers with high accuracy.Methods and analysis We collected plasma samples from 440 individuals, healthy and diagnosed with 18 early-stage solid tumours. Using proximity extension assay, we measured more than 3000 high-abundance and low-abundance proteins in each sample. Then, using a multi-step statistical approach, we identified a limited set of sex-specific proteins that could detect early-stage cancers and their tissue of origin with high accuracy.Results Our sex-specific cancer detection panels consisting of 10 proteins showed high accuracy for both males (area under the curve (AUC): 0.98, 95% CI 0.96, 1) and females (AUC: 0.983, 95% CI 0.95, 1.00). At stage I and at the specificity of 99%, our panels were able to identify 93% (95% CI 79%, 100%) of cancers among males and 84% (95% CI 68%, 100%) of cancers among females. Our sex-specific localisation panels consisted of 150 proteins and were able to identify the tissue of origin of most cancers in more than 80% of cases. The analysis of the plasma concentrations of proteins selected showed that almost all the proteins were in the low-concentration part of the human plasma proteome.Conclusion The proteome-based screening test showed promising performance compared with other technologies and could be a starting point for developing a new generation of screening tests for the early detection of cancer.