Evaluation of pre-diagnostic blood protein measurements for predicting survival after lung cancer diagnosis

• Published in: eBioMedicine
• Main Authors: Feng, Xiaoshuang, Muller, David C., Zahed, Hana, Alcala, Karine, Guida, Florence, Smith-Byrne, Karl, Yuan, Jian-Min, Koh, Woon-Puay, Wang, Renwei, Milne, Roger L., Bassett, Julie K., Langhammer, Arnulf, Hveem, Kristian, Stevens, Victoria L., Wang, Ying, Johansson, Mikael, Tjønneland, Anne, Tumino, Rosario, Sheikh, Mahdi, Johansson, Mattias, Robbins, Hilary A.
• Format: Text
• Language: English
• Published: Elsevier 2023
• Subjects: Articles; Inca; Northern Sweden
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232655/; https://doi.org/10.1016/j.ebiom.2023.104623

BACKGROUND: To evaluate whether circulating proteins are associated with survival after lung cancer diagnosis, and whether they can improve prediction of prognosis. METHODS: We measured up to 1159 proteins in blood samples from 708 participants in 6 cohorts. Samples were collected within 3 years prior to lung cancer diagnosis. We used Cox proportional hazards models to identify proteins associated with overall mortality after lung cancer diagnosis. To evaluate model performance, we used a round-robin approach in which models were fit in 5 cohorts and evaluated in the 6th cohort. Specifically, we fit a model including 5 proteins and clinical parameters and compared its performance with clinical parameters only. FINDINGS: There were 86 proteins nominally associated with mortality (p < 0.05), but only CDCP1 remained statistically significant after accounting for multiple testing (hazard ratio per standard deviation: 1.19, 95% CI: 1.10–1.30, unadjusted p = 0.00004). The external C-index for the protein-based model was 0.63 (95% CI: 0.61–0.66), compared with 0.62 (95% CI: 0.59–0.64) for the model with clinical parameters only. Inclusion of proteins did not provide a statistically significant improvement in discrimination (C-index difference: 0.015, 95% CI: −0.003 to 0.035). INTERPRETATION: Blood proteins measured within 3 years prior to lung cancer diagnosis were not strongly associated with lung cancer survival, nor did they importantly improve prediction of prognosis beyond clinical information. FUNDING: No explicit funding for this study. Authors and data collection supported by the US National Cancer Institute (U19CA203654), INCA (France, 2019-1-TABAC-01), 10.13039/100002002Cancer Research Foundation of Northern Sweden (AMP19-962), and Swedish Department of Health Ministry.