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

• Published in: eBioMedicine
• Main Authors: Feng, X, Muller, DC, Zahed, H, Alcala, K, Guida, F, Smith-Byrne, K, Yuan, J-M, Koh, W-P, Wang, R, Milne, RL, Bassett, JK, Langhammer, A, Hveem, K, Stevens, VL, Wang, Y, Johansson, M, Tjonneland, A, Tumino, R, Sheikh, M, Robbins, HA
• Format: Article in Journal/Newspaper
• Language: English
• Published: ELSEVIER 2023
• Subjects: Inca; Northern Sweden
• Online Access: http://hdl.handle.net/11343/332492

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), Cancer Research Foundation of Northern Sweden (AMP19-962), and Swedish Department of Health Ministry.