Glycometabolic, inflammatory and exocrine plasma proteins predict cancer in individuals with cardiovascular disease
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Cancer development is preceded by systemic immune, metabolic and tissue perturbation. We asked whether a minimal circulating-protein signature anticipates incident cancer in patients with atheromatous cardiovascular disease (ACVD) exposed to tobacco. Discovery used a nested case–control set drawn from the longitudinal FLEMENGHO cohort (n=156; 38 incident lung cancers). Multi-omic profiling returned a two-step classifier: four proteins, smoking status, personal cancer history. Preprocessing constants, classifiers and both thresholds were fixed before transfer to PREVALUNG (n=397; 58 incident cancers, 26 of them lung). There, low O-GlcNAcase (OGA) with low interleukin-6 (IL-6) defined a very-low-risk stratum holding 1 of 58 cancers (sensitivity 98.3%, negative predictive value 98.8%); low chymotrypsin C (CTRC) with high β-microseminoprotein (MSMB) defined a high-risk stratum in which 15 of 28 participants developed cancer. No additional omic feature — metabolomic, immunophenotypic, clonal-haematopoietic or metagenomic — was retained as a reproducible improvement to the classifier under our selection framework. Discrimination was greater for cancers diagnosed ≥12 months after sampling than for near-term cancers (AUC 0.766, 95% CI 0.671–0.857, versus 0.589, 0.485–0.692), arguing against performance being driven principally by occult disease. These estimates are conditional on the cancer frequency of this population. They require prospective confirmation before any imaging schedule is changed.
Authors: Marine Fidelle, David Boulate, Thao-Nguyen Pham, Antoine Giboudot, Louis Picq, Pamela Abdayem, Aline Renneville, Pauline Pradère, Caroline Caramella, Sylvère Durand, Fanny Aprahamian, Thibault Dayris, Marc Deloger, Nathalie Droin, Océane Hache, Magalie Martineau, Thierry Walzer, Olaf Mercier, Tatiana Kuznetsova, Laurence Zitvogel, Nikos Paragios, Guido Kroemer
Institutions: Inserm, Université Paris-Saclay, Aix-Marseille Université, Hôpital Nord, Hôpital Marie Lannelongue, Lyon 1 Université, École Normale Supérieure de Lyon, Centre National de la Recherche Scientifique, Université de Lyon, Centre International de Recherche en Infectiologie, Institut Gustave Roussy, Cellules souches hématopoïétiques et développement des hémopathies myéloïdes, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, KU Leuven, CentraleSupélec, Université Paris Cité, Sorbonne Université, Centre de Recherche des Cordeliers, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Association pour la Recherche sur le Cancer, Seerave Foundation, E-Rare, European Commission, Agence Nationale de la Recherche, Fondation Leducq, Institut National de la Santé et de la Recherche Médicale, Ligue Contre le Cancer, Institut Universitaire de France, Institut National Du Cancer, Institut Gustave-Roussy, Direction Générale de l’offre de Soins, European Research Area Network on Cardiovascular Diseases, HORIZON EUROPE Framework Programme, Labex Immuno-Oncology
Awards: G1056382719, G1085172537, G1397743473, G161558081, G1723499231, G1846858737, G1912211089, G2203660494, Biomarkers affecting the transition from cardiovascular disease to lung cancer: towards stratified interception., G2485135851, Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis and prediction of treatment response., G2699422577, G282393413, G3116448791, G3231222199, G3235171639, G3599999703, G3772543176, G3925730256, G4323719209, Regulation of ileal immune responses in the immunosurveillance of colon cancer: role of DAMPs, PAMPs, and self antigens., G4562215606, G4656594441, G4880911435, G4900465205, G528741065, G5474765000, G5644614043, G5767140378, G6300110603, G6318841463, G6610179393, G668953012, G7041469554, G7101784390, G7156242582, G7466508714, G7662726268, G7666431813, G816800923, G8312322146, G8471630636, Université de Paris, G8591183789
OpenAlex ID: W7212297968