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

Abstract

BackgroundEarly detection of cancer is crucial for reducing the global burden of cancer and saving lives, but effective screening tests for many cancers do not exist. Genomics-based liquid biopsy tests for screening multiple cancers at once have been developed, but they have low sensitivity for early-stage cancers and are expensive. Recent advancements in measuring protein abundances in plasma offer new opportunities for developing multi-cancer screening tests.MethodsWe collected plasma samples from 440 individuals, healthy and diagnosed with 18 various types of early-stage solid tumours. Using Proximity Extension Assay, we measured more than 3000 high and low-abundance proteins in each sample. Then, using a multi-step statistical approach, we identified a limited set of proteins that could detect early-stage cancers and their tissue of origin with high diagnostic accuracy.FindingsOur sex-specific cancer detection consisting of 10 proteins showed high accuracy for both males (AUC: 0.98) and females ((AUC: 0.983). At stage I and at the specificity of 99%, our detection panels were able to identify 89% of cancers among males and 75% of cancers among females.Our sex-specific localization 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.InterpretationThe 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 and potentially other chronic diseases. This new approach may provide a more accessible and cost-effective alternative to existing methods for cancer detection and may help reduce cancer mortality rates globally.