TY - JOUR
T1 - Quantitative targeted proteomics for occult cancer screening in patients with unprovoked venous thromboembolism
T2 - results from the prospective PLATO-VTE study
AU - Guman, Noori A.M.
AU - Kraaijpoel, Noémie
AU - Mulder, Frits I.
AU - Carrier, Marc
AU - Jara-Palomares, Luis
AU - Di Nisio, Marcello
AU - Ageno, Walter
AU - Beyer-Westendorf, Jan
AU - Klok, Frederikus A.
AU - Vanassche, Thomas
AU - Otten, Johannes M.M.B.
AU - Cosmi, Benilde
AU - Peters, Mike J.L.
AU - ten Wolde, Marije
AU - Delluc, Aurélien
AU - Kamphuisen, Pieter W.
AU - Sánchez-López, Verónica
AU - Porreca, Ettore
AU - Ramaker, Jip
AU - Bossuyt, Patrick M.M.
AU - Büller, Harry R.
AU - Versteeg, Henri H.
AU - van Vlijmen, Bart J.M.
AU - van Es, Nick
AU - Mohammed, Yassene
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/8
Y1 - 2025/8
N2 - Background: About 5% of patients with unprovoked venous thromboembolism (VTE) have occult cancer. Despite standard cancer screening, 50% of cancers remain undetected. Objectives: We used quantitative targeted proteomics to identify novel cancer biomarkers among patients with unprovoked VTE. Methods: Patients aged ≥40 years with a first unprovoked VTE and without a malignancy in the preceding 5 years were invited to an international prospective cohort study. Plasma samples were collected within 10 days after VTE. The primary outcome was an adjudicated cancer diagnosis during 12-month follow-up. Concentrations of 269 plasma proteins covering coagulation, complement, and cancer-associated pathways were measured using quantitative mass spectrometry-based targeted proteomics. In a nested case-control study, protein profiles of patients with cancer were compared with those of randomly sampled unique control patients (ratio 3:1). Proteins with an unadjusted P value < .05 and fold change ≥15% were combined in a multivariable logistic regression model. To address the variability in the obtained model, the protein selection and model-building approach were replicated in 250 bootstrap samples, and an optimism-adjusted c-statistic was calculated. Results: Of the 476 included participants, 28 (5.9%) were newly diagnosed with cancer. Plasma samples were available for 24 cases, which were compared with those of 75 control patients. Concentrations of P-selectin, β-2 microglobulin, complement component 7, intracellular adhesion molecule 1, and lumican were higher in cases than in controls, whereas coagulation factor (F)VII, FX, and FXII, β-Ala-His dipeptidase, and kalistatin were lower. The optimism-adjusted c-statistic of the multivariable logistic regression model including these proteins was 0.78 (95% CI, 0.70-0.87). Conclusion: Ten differentially abundant proteins were identified in patients with occult cancer, suggesting potential of plasma proteomic tests as novel biomarker for occult cancer in patients with unprovoked VTE.
AB - Background: About 5% of patients with unprovoked venous thromboembolism (VTE) have occult cancer. Despite standard cancer screening, 50% of cancers remain undetected. Objectives: We used quantitative targeted proteomics to identify novel cancer biomarkers among patients with unprovoked VTE. Methods: Patients aged ≥40 years with a first unprovoked VTE and without a malignancy in the preceding 5 years were invited to an international prospective cohort study. Plasma samples were collected within 10 days after VTE. The primary outcome was an adjudicated cancer diagnosis during 12-month follow-up. Concentrations of 269 plasma proteins covering coagulation, complement, and cancer-associated pathways were measured using quantitative mass spectrometry-based targeted proteomics. In a nested case-control study, protein profiles of patients with cancer were compared with those of randomly sampled unique control patients (ratio 3:1). Proteins with an unadjusted P value < .05 and fold change ≥15% were combined in a multivariable logistic regression model. To address the variability in the obtained model, the protein selection and model-building approach were replicated in 250 bootstrap samples, and an optimism-adjusted c-statistic was calculated. Results: Of the 476 included participants, 28 (5.9%) were newly diagnosed with cancer. Plasma samples were available for 24 cases, which were compared with those of 75 control patients. Concentrations of P-selectin, β-2 microglobulin, complement component 7, intracellular adhesion molecule 1, and lumican were higher in cases than in controls, whereas coagulation factor (F)VII, FX, and FXII, β-Ala-His dipeptidase, and kalistatin were lower. The optimism-adjusted c-statistic of the multivariable logistic regression model including these proteins was 0.78 (95% CI, 0.70-0.87). Conclusion: Ten differentially abundant proteins were identified in patients with occult cancer, suggesting potential of plasma proteomic tests as novel biomarker for occult cancer in patients with unprovoked VTE.
KW - early detection of cancer
KW - liquid biopsy
KW - neoplasms
KW - proteomics
KW - venous thromboembolism
UR - https://www.scopus.com/pages/publications/105015994534
U2 - 10.1016/j.rpth.2025.103018
DO - 10.1016/j.rpth.2025.103018
M3 - Article
AN - SCOPUS:105015994534
SN - 2475-0379
VL - 9
JO - Research and practice in thrombosis and haemostasis
JF - Research and practice in thrombosis and haemostasis
IS - 6
M1 - 103018
ER -