The blood proteome of imminent lung cancer diagnosis
Demetrius Albanes, Karine Alcala, Nicolas Alcala, Christopher I. Amos, Alan A. Arslan, Julie K. Bassett, Paul Brennan, Qiuyin Cai, Chu Chen, Xiaoshuang Feng, Neal D. Freedman, Florence Guida, Rayjean J. Hung, Kristian Hveem, Mikael Johansson, Mattias Johansson, Woon‐Puay Koh, Arnulf Langhammer, Roger L. Milne, David C. Muller, Justina Ucheojor Onwuka, Elin Pettersen Sørgjerd, Hilary A. Robbins, Howard D. Sesso, Gianluca Severi, Xiao-Ou Shu, Sabina Sieri, Karl Smith-Byrne, Victoria L. Stevens, Lesley F. Tinker, Anne Tjønneland, Kala Visvanathan, Ying Wang, Renwei Wang, Stephanie J. Weinstein, Jian‐Min Yuan, Hana Zahed, Xuehong Zhang, Wei Zheng, Xuehong Zhang, Wei Zheng
Abstract
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.