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

Xiaoshuang Feng, David C. Muller, Hana Zahed, Karine Alcala, Florence Guida, Karl Smith-Byrne, Jian Min Yuan, Woon Puay Koh, Renwei Wang, Roger L. Milne, Julie K. Bassett, Arnulf Langhammer, Kristian Hveem, Victoria L. Stevens, Ying Wang, Mikael Johansson, Anne Tjønneland, Rosario Tumino, Mahdi Sheikh, Mattias JohanssonHilary A. Robbins

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish (US)
JournalEBioMedicine
Volume92
DOIs
StatePublished - Jun 1 2023
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-09-21

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine

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