Novel proteomics-based plasma test for early detection of multiple cancers in the general population
Selected publication · BMJ Oncology, 2024
Budnik B., Amirkhani H., Forouzanfar M., Afshin A.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Oncology | Patient Stratification | Plasma |  Olink Explore 3072/384 |
Editor's note
This study by scientists from Novelna Inc. used the Olink Explore 3072 high-throughput protein biomarker discovery platform to look at the plasma profiles of over 3,000 proteins in individuals with 18 different types of early-stage solid tumors and healthy controls, with the aim of deriving high-performance biomarker signatures for early detection of multiple forms of cancer. Strikingly, there were marked sex-specific differences in the cancer-associated proteins, with ~80% of significant proteins in men showing no significant differences in women, and vice versa. Sex-specific 10-protein models were developed for both men and women and these identified 93% of cancers in men, and 84% in women.
Significantly larger multi-protein models were also derived to discriminate tumors derived from different tissues. While the numbers of proteins included and model performance varied according to tumor type, these signatures correctly identified the tissue of origin in 80% of cases. The authors concluded that “Our new generation protein-based plasma test has shown high sensitivity in detecting a variety of early-stage tumors in asymptomatic patients, making it a strong candidate for use as a population-wide screening tool that is not currently achievable with existing tests or techniques”.
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.