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

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  • 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
  • Rosario Tumino
  • Mahdi Sheikh
  • Mattias Johansson
  • Hilary A. Robbins

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
Article number104623
JournalEBioMedicine
Volume92
Number of pages11
ISSN2352-3964
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 World Health Organization

    Research areas

  • Lung cancer, Lung cancer prognosis, Lung cancer survival, Protein biomarkers

ID: 358229844