Evaluation of pre-diagnostic blood protein measurements for predicting survival after lung cancer diagnosis
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 104623 |
| Tidsskrift | EBioMedicine |
| Vol/bind | 92 |
| Antal sider | 11 |
| ISSN | 2352-3964 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We thank the Biobank Research Unit at Umeå University, Västerbotten Intervention Programme, the Northern Sweden MONICA study, the Mammography Study and Region Västerbotten for providing data and samples and acknowledge the contribution from Biobank Sweden, supported by the Swedish Research Council ( VR 2017-00650 ).
Funding Information:
The Singapore Chinese Health Study was supported by the US National Institutes of Health Grant No. R01CA080205 , R01CA144034 and UM182876 .
Funding Information:
The coordination of EPIC was financially supported by Direction Générale de la Santé (French Ministry of Health) (Grant GR-IARC-2003-09-12-01 ), the European Commission (Directorate General for Health and Consumer Affairs), International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics , School of Public Health, Imperial College London with additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer , Institut Gustave-Roussy , Mutuelle Générale de l'Education Nationale , Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid , German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro -AIRC-Italy, Compagnia di San Paolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds , Dutch Prevention Funds , Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Foundation (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía , Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK ( 14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study.
Funding Information:
The authors express sincere appreciation to all Cancer Prevention Study-II participants, and to each member of the study and biospecimen management group. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries and cancer registries supported by the National Cancer Institute's Surveillance Epidemiology and End Results Program .
Funding Information:
Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by by VicHealth and Cancer Council Victoria . The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057 , 396414 and 1074383 and by infrastructure provided by Cancer Council Victoria .
Funding Information:
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.The Trøndelag Health Study (HUNT) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology NTNU), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The Singapore Chinese Health Study was supported by the US National Institutes of Health Grant No. R01CA080205, R01CA144034 and UM182876. Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414 and 1074383 and by infrastructure provided by Cancer Council Victoria. The authors express sincere appreciation to all Cancer Prevention Study-II participants, and to each member of the study and biospecimen management group. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries and cancer registries supported by the National Cancer Institute's Surveillance Epidemiology and End Results Program. We thank the Biobank Research Unit at Umeå University, Västerbotten Intervention Programme, the Northern Sweden MONICA study, the Mammography Study and Region Västerbotten for providing data and samples and acknowledge the contribution from Biobank Sweden, supported by the Swedish Research Council (VR 2017-00650). The coordination of EPIC was financially supported by Direction Générale de la Santé (French Ministry of Health) (Grant GR-IARC-2003-09-12-01), the European Commission (Directorate General for Health and Consumer Affairs), International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London with additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di San Paolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Foundation (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study.
Publisher Copyright:
© 2023 World Health Organization
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