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Article ; Online: Suramin, a drug for the treatment of trypanosomiasis, reduces the prothrombotic and metastatic phenotypes of colorectal cancer cells by inhibiting hepsin.

Zaragoza-Huesca, David / Rodenas, Maria Carmen / Peñas-Martínez, Julia / Pardo-Sánchez, Irene / Peña-García, Jorge / Espín, Salvador / Ricote, Guillermo / Nieto, Andrés / García-Molina, Francisco / Vicente, Vicente / Lozano, Maria Luisa / Carmona-Bayonas, Alberto / Mulero, Victoriano / Pérez-Sánchez, Horacio / Martínez-Martínez, Irene

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 168, Page(s) 115814

Abstract: Recently, our group identified serine-protease hepsin from primary tumor as a biomarker of metastasis and thrombosis in patients with localized colorectal cancer. We described hepsin promotes invasion and thrombin generation of colorectal cancer cells in ...

Abstract	Recently, our group identified serine-protease hepsin from primary tumor as a biomarker of metastasis and thrombosis in patients with localized colorectal cancer. We described hepsin promotes invasion and thrombin generation of colorectal cancer cells in vitro and in vivo and identified venetoclax as a hepsin inhibitor that suppresses these effects. Now, we aspire to identify additional hepsin inhibitors, aiming to broaden the therapeutic choices for targeted intervention in colorectal cancer. Methods: We developed a virtual screening based on molecular docking between the hepsin active site and 2000 compounds from DrugBank. The most promising drug was validated in a hepsin activity assay. Subsequently, we measured the hepsin inhibitor effect on colorectal cancer cells with basal or overexpression of hepsin via wound-healing, gelatin matrix invasion, and plasma thrombin generation assays. Finally, a zebrafish model determined whether hepsin inhibition reduced the invasion of colorectal cancer cells overexpressing hepsin. Results: Suramin was the most potent hepsin inhibitor (docking score: -11.9691 Kcal/mol), with an IC50 of 0.66 µM. In Caco-2 cells with basal or overexpression of hepsin, suramin decreased migration and significantly reduced invasion and thrombin generation. Suramin did not reduce the thrombotic phenotype in the hepsin-negative colorectal cancer cells HCT-116 and DLD-1. Finally, suramin significantly reduced the in vivo invasion of Caco-2 cells overexpressing hepsin. Conclusion: Suramin is a novel hepsin inhibitor that reduces its protumorigenic and prothrombotic effects in colorectal cancer cells. This suggests the possibility of repurposing suramin and its derivatives to augment the repertoire of molecular targeted therapies against colorectal cancer.
MeSH term(s)	Animals ; Humans ; Suramin/pharmacology ; Suramin/therapeutic use ; Thrombin ; Caco-2 Cells ; Molecular Docking Simulation ; Zebrafish ; Phenotype ; Trypanosomiasis ; Colorectal Neoplasms/drug therapy
Chemical Substances	hepsin (EC 3.4.21.-) ; Suramin (6032D45BEM) ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2023-10-31
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.115814
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Article ; Online: Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors.

Zaragoza-Huesca, David / Martínez-Cortés, Carlos / Banegas-Luna, Antonio Jesús / Pérez-Garrido, Alfonso / Vegara-Meseguer, Josefina María / Peñas-Martínez, Julia / Rodenas, Maria Carmen / Espín, Salvador / Pérez-Sánchez, Horacio / Martínez-Martínez, Irene

International journal of molecular sciences

2022 Volume 23, Issue 5

Abstract: The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of ... ...

Abstract	The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.
MeSH term(s)	Amino Acid Chloromethyl Ketones/chemistry ; Amino Acid Chloromethyl Ketones/metabolism ; Amino Acid Chloromethyl Ketones/pharmacology ; COVID-19/transmission ; COVID-19/virology ; Catalytic Domain ; Cell Line, Tumor ; Cell Survival/drug effects ; Enoxaparin/chemistry ; Enoxaparin/metabolism ; Enoxaparin/pharmacology ; Furin/antagonists & inhibitors ; Furin/chemistry ; Furin/metabolism ; HEK293 Cells ; Humans ; Molecular Docking Simulation ; Molecular Structure ; Protease Inhibitors/chemistry ; Protease Inhibitors/metabolism ; Protease Inhibitors/pharmacology ; Proteolysis ; SARS-CoV-2/metabolism ; SARS-CoV-2/physiology ; Spermine/analogs & derivatives ; Spermine/chemistry ; Spermine/metabolism ; Spermine/pharmacology ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization ; Virus Replication ; Zeaxanthins/chemistry ; Zeaxanthins/metabolism ; Zeaxanthins/pharmacology
Chemical Substances	Amino Acid Chloromethyl Ketones ; Enoxaparin ; Protease Inhibitors ; Spike Glycoprotein, Coronavirus ; Zeaxanthins ; decanoylRVKRchloromethylketone ; kukoamine A ; spike protein, SARS-CoV-2 ; Spermine (2FZ7Y3VOQX) ; Furin (EC 3.4.21.75)
Language	English
Publishing date	2022-03-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23052796
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Article: Venetoclax is a potent hepsin inhibitor that reduces the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells.

Rodenas, Maria Carmen / Peñas-Martínez, Julia / Pardo-Sánchez, Irene / Zaragoza-Huesca, David / Ortega-Sabater, Carmen / Peña-García, Jorge / Espín, Salvador / Ricote, Guillermo / Montenegro, Sofía / Ayala-De La Peña, Francisco / Luengo-Gil, Ginés / Nieto, Andrés / García-Molina, Francisco / Vicente, Vicente / Bernardi, Francesco / Lozano, María Luisa / Mulero, Victoriano / Pérez-Sánchez, Horacio / Carmona-Bayonas, Alberto /

Martínez-Martínez, Irene

Frontiers in molecular biosciences

2023 Volume 10, Page(s) 1182925

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2023.1182925
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Article: Anti-Tumor Functions of Prelatent Antithrombin on Glioblastoma Multiforme Cells.

Peñas-Martínez, Julia / Luengo-Gil, Ginés / Espín, Salvador / Bohdan, Nataliya / Ortega-Sabater, Carmen / Ródenas, Maria Carmen / Zaragoza-Huesca, David / López-Andreo, María José / Plasencia, Carme / Vicente, Vicente / Carmona-Bayonas, Alberto / Martínez-Martínez, Irene

Biomedicines

2021 Volume 9, Issue 5

Abstract: Antithrombin, the main physiological inhibitor of the coagulation cascade, exerts anti-tumor effects on glioblastoma multiforme cells. Antithrombin has different conformations: native, heparin-activated, prelatent, latent, and cleaved. The prelatent form ...

Abstract	Antithrombin, the main physiological inhibitor of the coagulation cascade, exerts anti-tumor effects on glioblastoma multiforme cells. Antithrombin has different conformations: native, heparin-activated, prelatent, latent, and cleaved. The prelatent form has an intermediate affinity between latent and native antithrombin, although it is the most antiangiogenic form. Herein, we investigate the effect of this conformation on the tumorigenic processes of glioblastoma multiforme cells. Antithrombin forms were purified by chromatography. Chromogenic/fluorogenic assays were carried out to evaluate enteropeptidase and hepsin inhibition, two serine proteases involved in these processes. Wound healing, Matrigel invasion and BrdU incorporation assays were performed to study migration, invasion and proliferation. E-cadherin, Vimentin, VEGFA, pAKT, STAT3, pSTAT3, and pERK1/2 expression was assessed by Western blot and/or qRT-PCR. Prelatent antithrombin inhibited both enteropeptidase and hepsin, although it was less efficient than the native conformation. Exposure to prelatent antithrombin significantly reduced migration and invasion but not proliferation of U-87 MG, being the conformation most efficient on migration. Prelatent antithrombin down-regulated VEGFA, pSTAT3, and pERK1/2 expression in U-87 MG cells. Our work elucidates that prelatent antithrombin has surprisingly versatile anti-tumor properties in U-87 MG glioblastoma multiforme cells. This associates with resistance pathway activation, the decreased expression of tumorigenic proteins, and increased angiogenesis, postulating the existence of a new, formerly unknown receptor with potential therapeutic implications.
Language	English
Publishing date	2021-05-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9050523
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Article: Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients.

Zaragoza-Huesca, David / Nieto-Olivares, Andrés / García-Molina, Francisco / Ricote, Guillermo / Montenegro, Sofía / Sánchez-Cánovas, Manuel / Garrido-Rodríguez, Pedro / Peñas-Martínez, Julia / Vicente, Vicente / Martínez, Francisco / Lozano, María Luisa / Carmona-Bayonas, Alberto / Martínez-Martínez, Irene

Cancers

2022 Volume 14, Issue 13

Abstract: Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations ... ...

Abstract	Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases. Tissue microarrays were produced from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin expression was correlated with clinical-histopathological variables by using the chi-square and Kruskal−Wallis tests, Kaplan−Meier and Aalen−Johansen estimators, and Cox and Fine and Gray multivariate models. In localized cancer patients, high-intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). Medium and high intensity of hepsin expression versus low expression was associated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value = 0.035 and hazard ratio 3.30, p-value = 0.012, respectively), being a better prognostic factor than classic histological variables. Additionally, in patients with localized tumor, 5-year thrombosis cumulative incidence increased with the increment of hepsin expression (p-value = 0.038). Medium and high intensities of hepsin with respect to low intensity were associated with an increase in thrombotic risk (hazard ratio 7.71, p-value = 0.043 and hazard ratio 9.02, p-value = 0.028, respectively). This relationship was independent of previous tumor relapse (p-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (p-value < 0.001) and with major metastatic dissemination (p-value = 0.023). Hepsin is a potential thrombotic and metastatic biomarker in patients with localized colorectal cancer. In metastatic patients, hepsin behaves in a paradoxical way with respect to differentiation and invasion processes.
Language	English
Publishing date	2022-06-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14133106
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Article ; Online: Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors

David Zaragoza-Huesca / Carlos Martínez-Cortés / Antonio Jesús Banegas-Luna / Alfonso Pérez-Garrido / Josefina María Vegara-Meseguer / Julia Peñas-Martínez / Maria Carmen Rodenas / Salvador Espín / Horacio Pérez-Sánchez / Irene Martínez-Martínez

International Journal of Molecular Sciences, Vol 23, Iss 2796, p

2022 Volume 2796

Abstract	The endogenous protease furin is a key protein in many different diseases, such as cancer and infections. For this reason, a wide range of studies has focused on targeting furin from a therapeutic point of view. Our main objective consisted of identifying new compounds that could enlarge the furin inhibitor arsenal; secondarily, we assayed their adjuvant effect in combination with a known furin inhibitor, CMK, which avoids the SARS-CoV-2 S protein cleavage by means of that inhibition. Virtual screening was carried out to identify potential furin inhibitors. The inhibition of physiological and purified recombinant furin by screening selected compounds, Clexane, and these drugs in combination with CMK was assayed in fluorogenic tests by using a specific furin substrate. The effects of the selected inhibitors from virtual screening on cell viability (293T HEK cell line) were assayed by means of flow cytometry. Through virtual screening, Zeaxanthin and Kukoamine A were selected as the main potential furin inhibitors. In fluorogenic assays, these two compounds and Clexane inhibited both physiological and recombinant furin in a dose-dependent way. In addition, these compounds increased physiological furin inhibition by CMK, showing an adjuvant effect. In conclusion, we identified Kukoamine A, Zeaxanthin, and Clexane as new furin inhibitors. In addition, these drugs were able to increase furin inhibition by CMK, so they could also increase its efficiency when avoiding S protein proteolysis, which is essential for SARS-CoV-2 cell infection.
Keywords	furin ; virtual screening ; inhibitors ; CMK ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	540
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Identification of Thrombosis-Related Genes in Patients with Advanced Gastric Cancer: Data from AGAMENON-SEOM Registry.

Zaragoza-Huesca, David / Garrido-Rodríguez, Pedro / Jiménez-Fonseca, Paula / Martínez de Castro, Eva / Sánchez-Cánovas, Manuel / Visa, Laura / Custodio, Ana / Fernández-Montes, Ana / Peñas-Martínez, Julia / Morales Del Burgo, Patricia / Gallego, Javier / Luengo-Gil, Ginés / Vicente, Vicente / Martínez-Martínez, Irene / Carmona-Bayonas, Alberto

Biomedicines

2022 Volume 10, Issue 1

Abstract: Advanced gastric cancer is one of the most thrombogenic neoplasms. However, genetic mechanisms underlying this complication remain obscure, and the molecular and histological heterogeneity of this neoplasm hinder the identification of thrombotic ... ...

Abstract	Advanced gastric cancer is one of the most thrombogenic neoplasms. However, genetic mechanisms underlying this complication remain obscure, and the molecular and histological heterogeneity of this neoplasm hinder the identification of thrombotic biomarkers. Therefore, our main objective was to identify genes related to thrombosis regardless of Lauren subtypes. Furthermore, in a secondary exploratory study, we seek to discover thrombosis-associated genes that were specific to each TCGA molecular subtype. We designed a nested case-control study using the cohort of the AGAMENON national advanced gastric cancer registry. Ninety-seven patients were selected-48 with and 49 without venous thromboembolism (using propensity score matching to adjust for confounding factors)-and a differential gene expression array stratified by Lauren histopathological subtypes was carried out in primary tumor samples. For the secondary objective, the aforementioned differential expression analysis was conducted for each TCGA group. Fifteen genes were determined to be associated with thrombosis with the same expression trend in both the intestinal and diffuse subtypes. In thrombotic subjects,
Language	English
Publishing date	2022-01-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10010148
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Article ; Online: Venetoclax is a potent hepsin inhibitor that reduces the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells

Frontiers in Molecular Biosciences, Vol

2023 Volume 10

Abstract: Introduction: Hepsin is a type II transmembrane serine protease and its expression has been linked to greater tumorigenicity and worse prognosis in different tumors. Recently, our group demonstrated that high hepsin levels from primary tumor were ... ...

Abstract	Introduction: Hepsin is a type II transmembrane serine protease and its expression has been linked to greater tumorigenicity and worse prognosis in different tumors. Recently, our group demonstrated that high hepsin levels from primary tumor were associated with a higher risk of metastasis and thrombosis in localized colorectal cancer patients. This study aims to explore the molecular role of hepsin in colorectal cancer.Methods: Hepsin levels in plasma from resected and metastatic colorectal cancer patients were analyzed by ELISA. The effect of hepsin levels on cell migration, invasion, and proliferation, as well as on the activation of crucial cancer signaling pathways, was performed in vitro using colorectal cancer cells. A thrombin generation assay determined the procoagulant function of hepsin from these cells. A virtual screening of a database containing more than 2000 FDA-approved compounds was performed to screen hepsin inhibitors, and selected compounds were tested in vitro for their ability to suppress hepsin effects in colorectal cancer cells. Xenotransplantation assays were done in zebrafish larvae to study the impact of venetoclax on invasion promoted by hepsin.Results: Our results showed higher plasma hepsin levels in metastatic patients, among which, hepsin was higher in those suffering thrombosis. Hepsin overexpression increased colorectal cancer cell invasion, Erk1/2 and STAT3 phosphorylation, and thrombin generation in plasma. In addition, we identified venetoclax as a potent hepsin inhibitor that reduced the metastatic and prothrombotic phenotypes of hepsin-expressing colorectal cancer cells. Interestingly, pretreatment with Venetoclax of cells overexpressing hepsin reduced their invasiveness in vivo.Discussion: Our results demonstrate that hepsin overexpression correlates with a more aggressive and prothrombotic tumor phenotype. Likewise, they demonstrate the antitumor role of venetoclax as a hepsin inhibitor, laying the groundwork for molecular-targeted therapy for colorectal cancer.
Keywords	hepsin ; colorectal cancer ; metastasis ; thrombosis ; molecular-targeted therapy ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Anti-Tumor Functions of Prelatent Antithrombin on Glioblastoma Multiforme Cells

Julia Peñas-Martínez / Ginés Luengo-Gil / Salvador Espín / Nataliya Bohdan / Carmen Ortega-Sabater / Maria Carmen Ródenas / David Zaragoza-Huesca / María José López-Andreo / Carme Plasencia / Vicente Vicente / Alberto Carmona-Bayonas / Irene Martínez-Martínez

Biomedicines, Vol 9, Iss 523, p

2021 Volume 523

Abstract	Antithrombin, the main physiological inhibitor of the coagulation cascade, exerts anti-tumor effects on glioblastoma multiforme cells. Antithrombin has different conformations: native, heparin-activated, prelatent, latent, and cleaved. The prelatent form has an intermediate affinity between latent and native antithrombin, although it is the most antiangiogenic form. Herein, we investigate the effect of this conformation on the tumorigenic processes of glioblastoma multiforme cells. Antithrombin forms were purified by chromatography. Chromogenic/fluorogenic assays were carried out to evaluate enteropeptidase and hepsin inhibition, two serine proteases involved in these processes. Wound healing, Matrigel invasion and BrdU incorporation assays were performed to study migration, invasion and proliferation. E-cadherin, Vimentin, VEGFA, pAKT, STAT3, pSTAT3, and pERK1/2 expression was assessed by Western blot and/or qRT-PCR. Prelatent antithrombin inhibited both enteropeptidase and hepsin, although it was less efficient than the native conformation. Exposure to prelatent antithrombin significantly reduced migration and invasion but not proliferation of U-87 MG, being the conformation most efficient on migration. Prelatent antithrombin down-regulated VEGFA, pSTAT3, and pERK1/2 expression in U-87 MG cells. Our work elucidates that prelatent antithrombin has surprisingly versatile anti-tumor properties in U-87 MG glioblastoma multiforme cells. This associates with resistance pathway activation, the decreased expression of tumorigenic proteins, and increased angiogenesis, postulating the existence of a new, formerly unknown receptor with potential therapeutic implications.
Keywords	angiogenesis ; enteropeptidase ; hepsin ; prelatent antithrombin ; glioblastoma multiforme ; invasion ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification of Thrombosis-Related Genes in Patients with Advanced Gastric Cancer

David Zaragoza-Huesca / Pedro Garrido-Rodríguez / Paula Jiménez-Fonseca / Eva Martínez de Castro / Manuel Sánchez-Cánovas / Laura Visa / Ana Custodio / Ana Fernández-Montes / Julia Peñas-Martínez / Patricia Morales del Burgo / Javier Gallego / Ginés Luengo-Gil / Vicente Vicente / Irene Martínez-Martínez / Alberto Carmona-Bayonas

Biomedicines, Vol 10, Iss 148, p

Data from AGAMENON-SEOM Registry

2022 Volume 148

Abstract	Advanced gastric cancer is one of the most thrombogenic neoplasms. However, genetic mechanisms underlying this complication remain obscure, and the molecular and histological heterogeneity of this neoplasm hinder the identification of thrombotic biomarkers. Therefore, our main objective was to identify genes related to thrombosis regardless of Lauren subtypes. Furthermore, in a secondary exploratory study, we seek to discover thrombosis-associated genes that were specific to each TCGA molecular subtype. We designed a nested case-control study using the cohort of the AGAMENON national advanced gastric cancer registry. Ninety-seven patients were selected—48 with and 49 without venous thromboembolism (using propensity score matching to adjust for confounding factors)—and a differential gene expression array stratified by Lauren histopathological subtypes was carried out in primary tumor samples. For the secondary objective, the aforementioned differential expression analysis was conducted for each TCGA group. Fifteen genes were determined to be associated with thrombosis with the same expression trend in both the intestinal and diffuse subtypes. In thrombotic subjects, CRELD1 , KCNH8 , CRYGN , MAGEB16 , SAA1 , ARL11 , CCDC169 , TRMT61A , RIPPLY3 and PLA2G6 were underexpressed (adjusted- p < 0.05), while PRKD3 , MIR5683 , SDCBP , EPS8 and CDC45 were overexpressed (adjusted- p < 0.05), and correlated, by logistic regression, with lower or higher thrombotic risk, respectively, in the overall cohort. In each TCGA molecular subtype, we identified a series of genes differentially expressed in thrombosis that appear to be subtype-specific. We have identified several genes associated with venous thromboembolism in advanced gastric cancer that are common to Lauren intestinal and diffuse subtypes. Should these genetic factors be validated in the future, they could be complemented with existing clinical models to bolster the ability to predict thrombotic risk in individuals with advanced gastric adenocarcinoma.
Keywords	advanced gastric adenocarcinoma ; genetic factors ; subtypes ; stratification ; venous thromboembolism ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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