Von Willebrand factor and cancer; metastasis and coagulopathies

Patmore, Sean; Dhami, Sukhraj Pal Singh; O’Sullivan, Jamie M.

doi:10.1111/jth.14976

Cited by 70 publications

(76 citation statements)

References 97 publications

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“…Not only it helps platelets to be absorbed in damaged endothelium but also latest research displays its tumour angiogenesis, in ammation and metastasis potential. 42,43 . On the surface of tumour cells, several vWF receptors such as glycoprotein Ib, integrin αIIbβ3 and αVβ3 have been identi ed; however, a direct link between vWF and tumour cells has also been observed 44 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Hub Genes, Modules and Metabolic Pathways Associated With Lung Adenocarcinoma: A System Biology Approach

Roudi¹,

Beikzadeh²,

Roviello³

et al. 2020

Preprint

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Lung cancer is the most common and fatal malignant tumour worldwide with a five‐year overall survival rate of only 15%. Lung adenocarcinoma (LUAD) is a heterogeneous disease. The use of microarray datasets along with bioinformatics knowledge might help to clarify the expression profile of cancer, molecular markers for the initial screening of tumour and the underlying biological mechanisms. The present study is designed to identify differential expression genes and molecular mechanisms of LUAD compared to normal lung tissues using systems biology approaches.Methods Four GSE datasets (GSE75037, GSE63459, GSE32863 and GSE10072) were selected from the Gene Expression Omnibus (GEO) database. Data processing and meta-analysis were performed using the R statistical programming language, The differentially expressed genes (DEGs) associated with each stage were obtained. The common and unique DEGs between stages of LUAD and adjacent normal lung tissues were initiated by Venny tool. Common genes, including upregulated and downregulated genes, were then analyzed to a STRING database to obtain protein-protein interaction (PPI). STRING output was analyzed by MCODE and CytoHubba applications of Cytoscape to identify modules of co-expression and hub genes, respectively.Results The shared upregulated and downregulated DEGs among LUAD stages were 22 and 140 genes, respectively, when compared to normal lung tissues. Unique genes for each stage were also identified. The hub genes were PECAM1, TEK, CDH5, VWF and ANGPT1. Most of the top cluster genes were enriched for Gα(s) signalling events, GPCR ligand binding, class B/2 (Secretin family receptors), platelet activation, signalling and aggregation in the main three co-expression clusters. Most of the shared genes (16 genes) were enriched in the metabolic pathway of hemostasis. Meaningful signaling pathways for unique genes were found at each stage.Conclusions In the present study main three co-expression clusters, metabolic pathways and biological processes were identified to understand mechanisms underlying LUAD pathogenesis, development and progression at different stages. Unique upregulated and downregulated DEGs at each stage were identified with FERMT1 and SIX1 as specific early-stage diagnostic biomarkers for stage IB and IIB. 5 hub genes were observed, including PECAM1, TEK, CDH5, vWF and ANGPT1 which might be crucial for the onset and progression of LUAD.

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Section: Discussionmentioning

confidence: 99%

“…In many cancers, high levels of vWF have been reported in plasma and tumour microenvironment, indicating an advanced stage of the disease. vWF facilitates tumour cell growth by upregulating in ammatory signals, angiogenesis and vascular permeability 43 .…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes, Modules and Metabolic Pathways Associated With Lung Adenocarcinoma: A System Biology Approach

Roudi¹,

Beikzadeh²,

Roviello³

et al. 2020

Preprint

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“…Von W illebr and Fac tor s tr uc ture-func tion in the regulation of c ancer met as t asis Jamie O'Sullivan For reference, see Patmore et al 49…”

Section: Von W Illebr and F Ac Tor Modulates Adhesion Of Malaria-infec Ted Er Y Throc Y Tes To Endothelial Cells James S O' Donnellmentioning

confidence: 99%

Illustrated State‐of‐the‐Art Capsules of the ISTH 2021 Congress

Krishnaswamy

Ageno

Arabi³

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) was hosted virtually from Philadelphia July 17–21, 2021. The conference, now held annually, highlighted cutting‐edge advances in basic, population and clinical sciences of relevance to the Society. Despite being held virtually, the 2021 congress was of the same scope and quality as an annual meeting held in person. An added feature of the program is that talks streamed at the designated times will then be available on‐line for asynchronous viewing. The program included 77 State of the Art (SOA) talks, thematically grouped in 28 sessions, given by internationally recognized leaders in the field. The SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. The topics, across the main scientific themes of the congress, include Arterial Thromboembolism, Coagulation and Natural Anticoagulants, COVID‐19 and Coagulation, Diagnostics and Omics, Fibrinogen, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostasis in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Angiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the congress.

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“…Moreover, vWF secretion has been reported to contribute to the process of EMT (240), the secretion of pro-inflammatory cytokines, and vascular permeability (234). Several studies show vWFdependent cancer cell adhesion to the endothelium is mediated by integrin receptors and facilitates extravasation during metastasis (239,(241)(242)(243). It is tempting to speculate that autophagy plays a central role in mediating cancer-related thrombosis and metastasis by regulating vWF release from the activated endothelium.…”

Section: Coagulation Cascade and Autophagy In The Tumor Endotheliummentioning

confidence: 99%

“…Within the TME, endothelial autophagy regulation of coagulative factors may contribute to cancer progression and cancer-related thrombosis. Cancer cells promote the secretion of WPBs and vWF from ECs ( 237 , 238 ) and elevated plasmatic vWF correlate with tumor grade and metastasis ( 239 ). Moreover, vWF secretion has been reported to contribute to the process of EMT ( 240 ), the secretion of pro-inflammatory cytokines, and vascular permeability ( 234 ).…”

Section: Coagulation Cascade and Autophagy In The Tumor Microenvironmmentioning

confidence: 99%

Deciphering the Role of the Coagulation Cascade and Autophagy in Cancer-Related Thrombosis and Metastasis

et al. 2020

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Thrombotic complications are the second leading cause of death among oncology patients worldwide. Enhanced thrombogenesis has multiple origins and may result from a deregulation of megakaryocyte platelet production in the bone marrow, the synthesis of coagulation factors in the liver, and coagulation factor signaling upon cancer and the tumor microenvironment (TME). While a hypercoagulable state has been attributed to factors such as thrombocytosis, enhanced platelet aggregation and Tissue Factor (TF) expression on cancer cells, further reports have suggested that coagulation factors can enhance metastasis through increased endothelial-cancer cell adhesion and enhanced endothelial cell activation. Autophagy is highly associated with cancer survival as a double-edged sword, as can both inhibit and promote cancer progression. In this review, we shall dissect the crosstalk between the coagulation cascade and autophagic pathway and its possible role in metastasis and cancer-associated thrombosis formation. The signaling of the coagulation cascade through the autophagic pathway within the hematopoietic stem cells, the endothelial cell and the cancer cell are discussed. Relevant to the coagulation cascade, we also examine the role of autophagy-related pathways in cancer treatment. In this review, we aim to bring to light possible new areas of cancer investigation and elucidate strategies for future therapeutic intervention.

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Von Willebrand factor and cancer; metastasis and coagulopathies

Cited by 70 publications

References 97 publications

Identification of Hub Genes, Modules and Metabolic Pathways Associated With Lung Adenocarcinoma: A System Biology Approach

Identification of Hub Genes, Modules and Metabolic Pathways Associated With Lung Adenocarcinoma: A System Biology Approach

Illustrated State‐of‐the‐Art Capsules of the ISTH 2021 Congress

Deciphering the Role of the Coagulation Cascade and Autophagy in Cancer-Related Thrombosis and Metastasis

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