microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors
Open Access
- 11 June 2020
- Vol. 12 (6), 1536
- https://doi.org/10.3390/cancers12061536
Abstract
Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95% CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95% CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95% CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.Keywords
Funding Information
- Instituto de Salud Carlos III (PIE13/00046, PI14/00079, PI14/00512, FI14/00269, CPII15/00002, PI17/00495)
- Generalitat Valenciana (PrometeoII/2015/017, ACIF/2017/138)
- Ministero della Salute (GR-2011-02347854)
This publication has 65 references indexed in Scilit:
- MicroRNA in Human GliomaCancers, 2013
- Circulating Nucleosomes and Neutrophil Activation as Risk Factors for Deep Vein ThrombosisArteriosclerosis, Thrombosis, and Vascular Biology, 2013
- Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosisProceedings of the National Academy of Sciences of the United States of America, 2012
- MicroRNA miR-451 downregulates the PI3K/AKT pathway through CAB39 in human gliomaInternational Journal of Oncology, 2011
- miR-22 represses cancer progression by inducing cellular senescenceThe Journal of cell biology, 2011
- New Insights Into Cancer-Associated ThrombosisArteriosclerosis, Thrombosis, and Vascular Biology, 2009
- MicroRNAs: Target Recognition and Regulatory FunctionsCell, 2009
- Development and validation of a predictive model for chemotherapy-associated thrombosisBlood, 2008
- Tissue factor, angiogenesis and tumour progressionBreast Cancer Research, 2008
- The 2007 WHO Classification of Tumours of the Central Nervous SystemActa Neuropathologica, 2007