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High throughput Proteomic Profiling in Cancer-Associated VTE and Link to the Clinical Outcome

1Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, 2DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany, 3Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, 4Bayer AG, Wuppertal, Germany, 5Clinical Trials, Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, 6Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, the Netherlands, Maastricht, the Netherlands

Abstract Number: OC 10.4

Meeting: ISTH 2020 Congress

Theme: Venous Thromboembolism and Cardioembolism » Cancer Associated Thrombosis

Background: Cancer‐associated venous thromboembolism (CAT) remains one of the leading causes of morbidity and mortality in cancer patients. Specific biological targets for cancer individuals at risk for venous thromboembolism (VTE) are presently missing.

Aims: The aims of this study are to explore the protein signature in CAT compared to non-cancer VTE and to investigate the relation of cancer-related proteins with clinical outcome e.g. recurrent VTE and/or bleeding.

Methods: A total of 652 individuals with acute VTE from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism (GMP-VTE) Project, of which 82 subjects had cancer, were included in this analysis. The proteomic profile was investigated in EDTA plasma with proximity extension assay technology (Olink Biosciences, Uppsala, Sweden). Quantification of 444 unique proteins from Cardiovascular, Cardiometabolic, Inflammation and Immune Response panels were used for analysis. Least absolute shrinkage and selection operator (LASSO)-regularized logistic regression, adjusted for age, sex, clinical profile and therapy was used to identify most relevant proteins associated with CAT. Age and sex adjusted Cox regression with competing risks (mortality) established the link of the CAT-related proteins to clinical outcome.

Results: LASSO regression identified 69 variables (n= 60 were unique proteins) with an area under the curve (AUC) of 0.89 (10-fold cross-validated AUC: 0.66) for differentiating CAT from non-cancer VTE. The identified proteins were primarily related to the immune response including interleukin and cytokine signaling, angiogenesis, cell growth regulation, complement and coagulation pathways. Monocyte chemoattractant protein (MCP)-1 was associated with less recurrent VTE in cancer subjects with HR=0.46 (0.29-0.72), p=0.0007. Additionally, transcription regulator protein BACH-1 was linked to less incident bleeding in cancer (HR=0.56 [0.41-0.76], p=0.0003).

Conclusions: CAT subjects presented with different humoral proteomic patterns compared to non-cancer VTE, independent of clinical risk factors and therapy. MCP-1 and BACH-1 were linked with better clinical outcome in cancer patients.

To cite this abstract in AMA style:

Panova-Noeva M, Schulz A, Köck T, ten Cate V, Wagner B, Rapp S, Prochaska J, Sauer M, Zink A, Ghadessi M, Konstantinides S, ten Cate H, Heitmeier S, Wild P. High throughput Proteomic Profiling in Cancer-Associated VTE and Link to the Clinical Outcome [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/high-throughput-proteomic-profiling-in-cancer-associated-vte-and-link-to-the-clinical-outcome/. Accessed September 29, 2023.

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