| Literature DB >> 33574093 |
Sonia Dagnino1, Barbara Bodinier1, Florence Guida2, Karl Smith-Byrne2, Dusan Petrovic1,3,4, Matthew D Whitaker1, Therese Haugdahl Nøst5, Claudia Agnoli6, Domenico Palli7, Carlotta Sacerdote8, Salvatore Panico9, Rosario Tumino10, Matthias B Schulze11,12, Mikael Johansson13, Pekka Keski-Rahkonen2, Augustin Scalbert2, Paolo Vineis1,14, Mattias Johansson2, Torkjel M Sandanger5, Roel C H Vermeulen1,15, Marc Chadeau-Hyam16,15.
Abstract
Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 prediagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared with controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels of CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/β-catenin pathway. Overall, this study identifies lung cancer-related dysregulation of CDCP1 expression years before diagnosis. SIGNIFICANCE: Prospective proteomics analyses reveal an association between increased levels of circulating CDCP1 and lung carcinogenesis irrespective of smoking and years before diagnosis, and integrating gene expression indicates potential underlying mechanisms.See related commentary by Itzstein et al., p. 3441. ©2021 American Association for Cancer Research.Entities:
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Year: 2021 PMID： 33574093 PMCID： PMC7611235 DOI： 10.1158/0008-5472.CAN-20-3454
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 13.312