Alterations of the Platelet Proteome in Lung Cancer: Accelerated F13A1 and ER Processing as New Actors in Hypercoagulability
In order to comprehensively expose cancer-related biochemical changes, we compared the platelet proteome of two types of cancer with a high risk of thrombosis (22 patients with brain cancer, 19 with lung cancer) to 41 matched healthy controls using unbiased two-dimensional differential in-gel electr...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/9/2260 |
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| author | Huriye Ercan Lisa-Marie Mauracher Ella Grilz Lena Hell Roland Hellinger Johannes A. Schmid Florian Moik Cihan Ay Ingrid Pabinger Maria Zellner |
| author_facet | Huriye Ercan Lisa-Marie Mauracher Ella Grilz Lena Hell Roland Hellinger Johannes A. Schmid Florian Moik Cihan Ay Ingrid Pabinger Maria Zellner |
| author_sort | Huriye Ercan |
| collection | DOAJ |
| description | In order to comprehensively expose cancer-related biochemical changes, we compared the platelet proteome of two types of cancer with a high risk of thrombosis (22 patients with brain cancer, 19 with lung cancer) to 41 matched healthy controls using unbiased two-dimensional differential in-gel electrophoresis. The examined platelet proteome was unchanged in patients with brain cancer, but considerably affected in lung cancer with 15 significantly altered proteins. Amongst these, the endoplasmic reticulum (ER) proteins calreticulin (CALR), endoplasmic reticulum chaperone BiP (HSPA5) and protein disulfide-isomerase (P4HB) were significantly elevated. Accelerated conversion of the fibrin stabilising factor XIII was detected in platelets of patients with lung cancer by elevated levels of a coagulation factor XIII (F13A1) 55 kDa fragment. A significant correlation of this F13A1 cleavage product with plasma levels of the plasmin–α-2-antiplasmin complex and D-dimer suggests its enhanced degradation by the fibrinolytic system. Protein association network analysis showed that lung cancer-related proteins were involved in platelet degranulation and upregulated ER protein processing. As a possible outcome, plasma FVIII, an immediate end product for ER-mediated glycosylation, correlated significantly with the ER-executing chaperones CALR and HSPA5. These new data on the differential behaviour of platelets in various cancers revealed F13A1 and ER chaperones as potential novel diagnostic and therapeutic targets in lung cancer patients. |
| first_indexed | 2024-03-10T11:37:04Z |
| format | Article |
| id | doaj.art-ecdd1138e25742eaa14015b2b4b24c4f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:37:04Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ecdd1138e25742eaa14015b2b4b24c4f2023-11-21T18:47:58ZengMDPI AGCancers2072-66942021-05-01139226010.3390/cancers13092260Alterations of the Platelet Proteome in Lung Cancer: Accelerated F13A1 and ER Processing as New Actors in HypercoagulabilityHuriye Ercan0Lisa-Marie Mauracher1Ella Grilz2Lena Hell3Roland Hellinger4Johannes A. Schmid5Florian Moik6Cihan Ay7Ingrid Pabinger8Maria Zellner9Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaCentre for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaCentre for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, 1090 Vienna, AustriaClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaClinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, AustriaCentre for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, 1090 Vienna, AustriaIn order to comprehensively expose cancer-related biochemical changes, we compared the platelet proteome of two types of cancer with a high risk of thrombosis (22 patients with brain cancer, 19 with lung cancer) to 41 matched healthy controls using unbiased two-dimensional differential in-gel electrophoresis. The examined platelet proteome was unchanged in patients with brain cancer, but considerably affected in lung cancer with 15 significantly altered proteins. Amongst these, the endoplasmic reticulum (ER) proteins calreticulin (CALR), endoplasmic reticulum chaperone BiP (HSPA5) and protein disulfide-isomerase (P4HB) were significantly elevated. Accelerated conversion of the fibrin stabilising factor XIII was detected in platelets of patients with lung cancer by elevated levels of a coagulation factor XIII (F13A1) 55 kDa fragment. A significant correlation of this F13A1 cleavage product with plasma levels of the plasmin–α-2-antiplasmin complex and D-dimer suggests its enhanced degradation by the fibrinolytic system. Protein association network analysis showed that lung cancer-related proteins were involved in platelet degranulation and upregulated ER protein processing. As a possible outcome, plasma FVIII, an immediate end product for ER-mediated glycosylation, correlated significantly with the ER-executing chaperones CALR and HSPA5. These new data on the differential behaviour of platelets in various cancers revealed F13A1 and ER chaperones as potential novel diagnostic and therapeutic targets in lung cancer patients.https://www.mdpi.com/2072-6694/13/9/2260cancerlung cancerthrombosisplateletsproteomicscoagulation factor XIII |
| spellingShingle | Huriye Ercan Lisa-Marie Mauracher Ella Grilz Lena Hell Roland Hellinger Johannes A. Schmid Florian Moik Cihan Ay Ingrid Pabinger Maria Zellner Alterations of the Platelet Proteome in Lung Cancer: Accelerated F13A1 and ER Processing as New Actors in Hypercoagulability Cancers cancer lung cancer thrombosis platelets proteomics coagulation factor XIII |
| title | Alterations of the Platelet Proteome in Lung Cancer: Accelerated F13A1 and ER Processing as New Actors in Hypercoagulability |
| title_full | Alterations of the Platelet Proteome in Lung Cancer: Accelerated F13A1 and ER Processing as New Actors in Hypercoagulability |
| title_fullStr | Alterations of the Platelet Proteome in Lung Cancer: Accelerated F13A1 and ER Processing as New Actors in Hypercoagulability |
| title_full_unstemmed | Alterations of the Platelet Proteome in Lung Cancer: Accelerated F13A1 and ER Processing as New Actors in Hypercoagulability |
| title_short | Alterations of the Platelet Proteome in Lung Cancer: Accelerated F13A1 and ER Processing as New Actors in Hypercoagulability |
| title_sort | alterations of the platelet proteome in lung cancer accelerated f13a1 and er processing as new actors in hypercoagulability |
| topic | cancer lung cancer thrombosis platelets proteomics coagulation factor XIII |
| url | https://www.mdpi.com/2072-6694/13/9/2260 |
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