&lt;p&gt;Clinical Significance of Factor XIII Activity and Monocyte-Derived Microparticles in Cancer Patients&lt;/p&gt;

Sawai, Yusuke; Yamanaka, Yutaka; Nomura, Shosaku

doi:10.2147/vhrm.s240500

Cited by 8 publications

(5 citation statements)

References 51 publications

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“…TGM1 was also upregulated in tumor cell aggregates (spheroids) exhibiting low chemosensitivity in ovarian cancer peritoneal uid (43). F13A1 has been identi ed as biomarkers of dismal prognosis in various types of cancers (35,44,45) and promotes the metastasis of melanoma as well as lung squamous cell carcinoma(46, 47). As a well-characterized transamidase, TGM2 can not only promote protein cross-linking by catalyzing post-translational modi cations of proteins, but also function as a G-protein coupled membrane receptor (GTPase), deamidase, adapter/scaffold, protein disul de isomerase, isopeptidase, and kinase (24,(48)(49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

Transglutaminases are oncogenic biomarkers in human cancers and therapeutic targeting of TGM2 blocks chemoresistance and macrophage infiltration in pancreatic cancer

Zhang

Yao

et al. 2023

Cell Oncol.

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Backgroud:Transglutaminases (TGs) are multifunctional enzymes with transglutaminase cross-linking, atypical GTPase/ATPase and kinase activity. Here, an integrated comprehensive analysis shows the genomic, transcriptomic and immunological landscapes of the TGs varies among different cancers. MethodsGene expression pattern and immune cell in ltration in pan-cancer were obtained from The Cancer Genome Atlas (TCGA) databases and Gene Set Enrichment Analysis (GSEA) datasets. Western blotting, immuno uorescence, ELISA, and orthotopic xenograft model were performed to validate our databasederived results. ResultsThe overall expression of TGs (designated as TG score) is signi cantly upregulated in multiple cancers and related to worse patient survial. The expression of the TG family can be regulated by multiple mechanisms at the genetic, epigenetic and transcriptional levels. Transcriptionfactors crucial for epithelial to mesenchymal transition (EMT) are commonly correlated with TG score in many cancer types.Importantly, TGM2 expression displays a close connection with the chemoresistances of a wide range of chemodrugs. TGM2, F13A1 and overall TG score are positively correlated with the in ltration of immune cells in all cancer types tested. Functional and clinical veri cation reveals that higher TGM2 expression is linked with worse patient survival, increased IC 50 value of gemcitabine, and abundant tumor-in ltrating macrophages in pancreatic cancer. Mechanistically, increased C-C motif chemokine ligand 2 (CCL2) release affored by TGM2 contributes to macrophage in ltration with tumor microenvironment. ConclusionsThese results reveal the relevances and molecular networks of TG genes in human cancers, highlighting the signi cance of TGM2 in pancreatic cancer which may provide some promising directions for immunotherapy and dealing with chemoresistance.

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Section: Discussionmentioning

confidence: 99%

Transglutaminases are oncogenic biomarkers in human cancers and therapeutic targeting of TGM2 blocks chemoresistance and macrophage infiltration in pancreatic cancer

Zhang

Yao

et al. 2023

Cell Oncol.

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“…Conventionally, a decrease in plasma factor XIIIa suggests a quantitative biomarker dynamics deviation towards hypocoagulability, i.e a reduced potential for the stabilization of fibrins in the final step of the coagulation pathway; however, factor XIIIa deficiency classification is not met until percent activity declines to less than 1%. 33,34 Thus, despite significant differences among the two groups, the relatively preserved percent activity of factor XIIIa within the lymphoma group suggests adequate clot stabilization potential, however, there is an inherent lack in previous studies which have explored this phenomenon in lymphoma patients. Limited data generated by Adany et al suggested tumorassociated macrophages containing factor XIII to exist as a nonhomogeneous population with varying protein expressivity.…”

Section: Thrombo-inflammatory Biomarkersmentioning

confidence: 99%

The Relationship Between Thrombo-Inflammatory Biomarkers and Cellular Indices of Inflammation in Lymphoma Patients

Jaradeh

Baig

Bontekoe

et al. 2021

Clin Appl Thromb Hemost

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Introduction Thrombo-inflammatory biomarkers play an important role in the pathogenesis of lymphoma. We aimed to characterize the interrelationship of thrombo-inflammatory biomarkers and blood cellular indices in lymphoma patients. Materials and Methods Ninety-eight lymphoma patient samples were collected from Lymphoma Center of Clinic of Hematology, University of Belgrade, Serbia. Normal controls (n = 50) represented plasma from healthy individuals. Plasminogen activator inhibitor (PAI-1), D-Dimer, factor XIII, C-reactive protein (CRP), microparticles (Mp), Von Willebrand factor (vWF), total protein S, urokinase-type plasminogen activator (uPA), tumor necrosis factor (TNF α), β2-glycoprotein I ( β2GPI), and fibronectin levels were measured utilizing commercially-available ELISA methods. Thrombin generation profile (TGA) was measured using a fluorometric kinetic assay. Platelets, leukocytes, lymphocytes, and neutrophils were measured in conjunction with the complete blood profile. Results Statistically significant differences were noted in levels of PAI-1, D-Dimer, factor XIII, CRP, microparticles, vWF, uPA, TNF α, β2GPI, fibronectin, and TGA when compared to normal (all P values < .001). Platelet to leukocyte ratio (PLA) correlated to TNF α and fibronectin ( R = −0.31 and −0.53, respectively) and the platelet to neutrophil ratio (PNR) correlated to factor XIII and β2GPI ( R = 0.40 and 0.40, respectively). Conclusion Plasma samples from lymphoma patients demonstrated a significantly altered thrombo-inflammatory biomarker profile that has notable correlations to blood cellular indices.

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“…Coagulation abnormalities are common in patients with metastatic oncological disease [13]. The relationship between FXIII and NSCLC is controversial, with some authors describing an increased activity of FXIII in patients with this neoplasm [7,8]. Given the initial picture of priapism in a patient with NSCLC, there was a suspicion of disseminated intravascular coagulation (DIC).…”

Section: Globalize Your Researchmentioning

confidence: 99%

“…The relationship between FXIII and non-small cell lung cancer (NSCLC) is controversial, with some authors describing an increased activity of FXIII in such cases [7,8]. This is a case report of a male patient with metastatic NSCLC and FXIII deficiency, which is a challenging diagnosis that requires a high index of clinical suspicion in the presence of normal routine coagulation tests (APTT, PT and fibrinogen).…”

Section: Introductionmentioning

confidence: 99%

Acquired Factor XIII Deficiency in a Patient with Metastatic Lung Cancer

Mendes¹,

Dias²,

Moráis³

et al. 2022

CORR

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Acquired factor XIII (FXIII) deficiency can result in life-long bleeding tendency and can be caused by enhanced consumption, impaired synthesis, or as an immune-mediated process. The latter can be related with solid neoplasms, through neutralizing or non-neutralizing antibodies. The relationship between FXIII activity and non-small cell lung cancer (NSCLC) is not well established. This case report is about a patient with NSCLC and acquired FXIII deficiency. Materials and Methods: Clinical records were obtained through the electronic process analysis, and the confidentiality of the patient was always assured. Results and Discussion: A 70-year-old male with no relevant past medical history and a recently diagnosed metastatic NSCLC was admitted for priapism. Five days later, a he developed a bleeding disorder, with slightly elevated coagulation times and normal fibrinogen levels and platelets count. FXIII level was found to be decreased (0.24 IU/mL) and FXIII plasma mixing studies did not confirm the presence of a neutralizing inhibitor. The FXIII level correction with standard plasma mixing studies was in favour of a non-neutralizing antibody. Despite treatment, haemorrhage control was not achieved and the patient died. Conclusion: This clinical report describes a rare case of a patient with metastatic NSCLC presenting a severe haemorrhagic event caused by FXIII deficiency immune-mediated by non-neutralizing antibodies and subsequent increased clearance.

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<p>Clinical Significance of Factor XIII Activity and Monocyte-Derived Microparticles in Cancer Patients</p>

Cited by 8 publications

References 51 publications

Transglutaminases are oncogenic biomarkers in human cancers and therapeutic targeting of TGM2 blocks chemoresistance and macrophage infiltration in pancreatic cancer

Transglutaminases are oncogenic biomarkers in human cancers and therapeutic targeting of TGM2 blocks chemoresistance and macrophage infiltration in pancreatic cancer

The Relationship Between Thrombo-Inflammatory Biomarkers and Cellular Indices of Inflammation in Lymphoma Patients

Acquired Factor XIII Deficiency in a Patient with Metastatic Lung Cancer

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