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The blood proteome of imminent lung cancer diagnosis

Nature Communications, 2023

Albanes D., Alcala K., Alcala N., Amos C., Arslan A., Bassett J., Brennan P., Cai Q., Chen C., Feng X., Freedman N., Guida F., Hung R., Hveem K., Johansson M., Johansson M., Koh W., Langhammer A., Milne R., Muller D., Onwuka J., Sørgjerd E., Robbins H., Sesso H., Severi G., Shu X., Sieri S., Smith-Byrne K., Stevens V., Tinker L., Tjønneland A., Visvanathan K., Wang Y., Wang R., Weinstein S., Yuan J., Zahed H., Zhang X., Zheng W.

Disease areaApplication areaSample typeProducts
Oncology
Pathophysiology
Patient Stratification
Plasma
Serum
Olink Target 96

Olink Target 96

Abstract

Identification of risk biomarkers may enhance early detection of smoking-related lung cancer. We measured between 392 and 1,162 proteins in blood samples drawn at most three years before diagnosis in 731 smoking-matched case-control sets nested within six prospective cohorts from the US, Europe, Singapore, and Australia. We identify 36 proteins with independently reproducible associations with risk of imminent lung cancer diagnosis (all p < 4 × 10−5). These include a few markers (e.g. CA-125/MUC-16 and CEACAM5/CEA) that have previously been reported in studies using pre-diagnostic blood samples for lung cancer. The 36 proteins include several growth factors (e.g. HGF, IGFBP-1, IGFP-2), tumor necrosis factor-receptors (e.g. TNFRSF6B, TNFRSF13B), and chemokines and cytokines (e.g. CXL17, GDF-15, SCF). The odds ratio per standard deviation range from 1.31 for IGFBP-1 (95% CI: 1.17–1.47) to 2.43 for CEACAM5 (95% CI: 2.04–2.89). We map the 36 proteins to the hallmarks of cancer and find that activation of invasion and metastasis, proliferative signaling, tumor-promoting inflammation, and angiogenesis are most frequently implicated.

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