Population-scale plasma proteomics reveals pre-diagnostic biomarkers and shared pathways of cancer risk across 25 cancers
Yarmolinsky, J.; Viallon, V.; Burk, V. A.; Muller, D. C.; Kolijn, P. M.; Lill, C. M.; Tsilidis, K.; Ferrari, P.; Richenberg, G.; Wang, Z.; Chirlaque Lopez, M. D.; Jimenez-Zabala, A.; Turmino, R.; Sacerdote, C.; Wareham, N.; Huang, Z.; Smith-Byrne, K.; Travis, R.; Chatterjee, N.; Platz, E. A.; Vermeulen, R. C.; Riboli, E.; Gunter, M. J.
Show abstract
The causes of most cancers remain unknown because the biological pathways underlying cancer development are poorly understood. Large-scale plasma proteomics offers a powerful strategy to uncover these pathways, identify biomarkers for cancer early detection, and discover novel therapeutic targets but has rarely been applied in prospective cohorts. Here, we profiled 6,402 plasma proteins using the SomaScanTM 7K Assay in baseline samples from 9,828 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC), including 6,073 incident cancer cases within a case-cohort design. We identified 1,732 protein-cancer associations (FDR P < 0.05) across 25 cancer endpoints in multivariable-adjusted models, including 60 proteins associated with overall cancer risk. Confirmation analyses in the Atherosclerosis Risk in Communities (ARIC) Study cohort showed directional concordance for 78% of associations and statistical replication of 49% of findings. Most proteins were associated with a single cancer type, whereas 284 were associated with multiple cancers, indicating both shared and distinct biological pathways across cancer sites. Stratification by follow-up time revealed 523 protein associations that were restricted to specific time windows after blood collection (<2 years, <5 years, and >5 years), including 447 that were not apparent in primary analyses, highlighting proteins with potential roles as early detection or aetiological biomarkers. Proteins associated with cancer risk were enriched across diverse biological pathways and 315 corresponded to targets of approved cancer and non-cancer medications, while most proteins represent previously unrecognised links to cancer risk. As the most comprehensive prospective investigation of the plasma proteome and cancer risk to date, our study significantly expands our understanding of key biological pathways shaping cancer development and provides a resource for the scientific community to accelerate development of early detection strategies, biomarkers for risk stratification, and novel therapeutic interventions for cancer prevention.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Systematic discovery of gene-environment interactions underlying the human plasma proteome in UK Biobank 94%
- Acute exercise rewires the proteomic landscape of human immune cells 93%
- Pan-cancer analysis demonstrates that integrating polygenic risk scores with modifiable risk factors improves risk prediction 93%
Similar papers in this journal
- Mammary epithelial cells have lineage-restricted metabolic identities 92%
- Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression 91%
- Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue 91%
Similar papers in this journal
- HIF2-driven PTHrP Causes Cachexia and Hypercalcemia in Kidney Cancer: Treatment with HIF2 Inhibitors 92%
- Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populations 91%
- A Neanderthal OAS1 isoform Protects Against COVID-19 Susceptibility and Severity: Results from Mendelian Randomization and Case-Control Studies 90%
Similar papers in this journal
- A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance 92%
- A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes 91%
- Serum proteomic profiling of physical activity reveals CD300LG as a novel exerkine with a potential causal link to glucose homeostasis 91%
Similar papers in this journal
- Deep plasma proteomics identifies and validates an eight-protein biomarker panel that separate benign from malignant tumors in ovarian cancer 92%
- Leveraging sequences missing from the human genome to diagnose cancer 91%
- Minimal Correlation but Complementary Diagnostic Utility for Plasma Cell-free RNA and Proteins 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.