Elevated ratio of C-type lectin-like receptor 2 level and platelet count (C2PAC) aids in the diagnosis of post-operative venous thromboembolism in IDH-wildtype gliomas

Ando, Kazuhiro; Natsumeda, Manabu; Kawamura, M.; Shirakawa, Kamon; Okada, Masayasu; Tsukamoto, Yoshihiro; Eda, Takeyoshi; Watanabe, Jun; Shoji, Shuichi; Takahashi, Hidemi; Kakita, Akiyoshi; Oishi, Makoto; Fujii, Yukihiko

doi:10.1016/j.thromres.2023.01.018

Cited by 9 publications

(21 citation statements)

References 23 publications

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“…Patients with ischemic stroke, acute coronary syndrome or coronary artery disease showed increased plasma concentration of soluble CLEC-2 (sCLEC-2) [16][17][18]. Similar observations were reported for patients with colorectal cancer (CRC) or glioma [19,20]. It was hypothesized that sCLEC-2 is released upon platelet activation and, therefore, sCLEC-2 could serve as a plasma biomarker of platelet activation [21].…”

Section: Introductionmentioning

confidence: 62%

C-Type Lectin-like Receptor 2 Expression Is Decreased upon Platelet Activation and Is Lower in Most Tumor Entities Compared to Healthy Controls

Etemad,

Christodoulou,

Uhlig

et al. 2023

Preprint

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The C-type lectin-like receptor 2 (CLEC-2) is expressed on platelets and mediates binding to podoplanin (PDPN) on various cell types. The binding to circulating tumor cells (CTCs) leads to platelet activation and promote metastatic spread. The increased level of soluble CLEC-2 (sCLEC-2), presumably, released from activated platelets was shown in patients with thromboinflammatory and malignant disease. However, the functional role of sCLEC-2 and the mechanism of sCLEC-2 release is not known. In this study, we focused on the effect of platelet activation on CLEC-2 expression and the sCLEC-2 plasma level in cancer patients. First, citrated blood from healthy volunteer donors (n=20) was used to measure the effect of platelet stimulation by classical agonists and PDPN on aggregation, CLEC-2 expression on platelets by flow cytometry, sCLEC-2 release to the plasma by ELISA and total CLEC-2 expression by Western blot analysis. Second, sCLEC-2 was determined in plasma samples from healthy donors (285) and patients with colorectal carcinoma (CRC; 194), melanoma (160), breast cancer (BC; 99) or glioblastoma (49). PDPN caused a significant increase of the aggregation response induced by classical agonists. ADP or PDPN stimulation of platelets caused a significant decrease of CLEC-2 on platelets and sCLEC-2 in the plasma, whereas, total CLEC-2 in platelet lysates remained the same. Thus, the increased plasma level of sCLEC-2 is not a suitable biomarker of platelet activation. In patients with CRC (median 0.9 ng/mL), melanoma (0.9 ng/mL) or BC (0.7 ng/mL) we found significantly lower sCLEC-2 levels (p&lt;0.0001), whereas, glioblastoma patients displayed higher levels (2.6 ng/mL; p=0.0233) compared to healthy controls (2.1 ng/mL). The low sCLEC-2 plasma level observed in most of the tumor entities of our study, presumably, results from the internalization of sCLEC-2 by activated platelets or binding of sCLEC-2 to CTC.

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Section: Introductionmentioning

confidence: 62%

C-Type Lectin-like Receptor 2 Expression Is Decreased upon Platelet Activation and Is Lower in Most Tumor Entities Compared to Healthy Controls

Etemad,

Christodoulou,

Uhlig

et al. 2023

Preprint

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“…45 For example, a correlation between sCLEC-2 (soluble C-type lectin-like receptor 2) levels and podoplanin expression has recently been established in patients with high-grade gliomas. 42 A relevant relationship between sCLEC-2 levels and the occurrence of CAT was demonstrated among these patients suggesting that podoplanin could be a potential marker to predict CAT in this patient population. 42…”

Section: Highlightsmentioning

confidence: 79%

“…42 A relevant relationship between sCLEC-2 levels and the occurrence of CAT was demonstrated among these patients suggesting that podoplanin could be a potential marker to predict CAT in this patient population. 42…”

Section: Highlightsmentioning

confidence: 79%

“…The current data suggest that there may be cancer typespecific pathways of VTE. 41 Therefore, the understanding of the pathogenesis of CAT is important and can lead to the identification of biomarkers helping clinicians to identify patients with cancer at high risk of VTE and potentially eligible for primary prevention [42][43][44] and those with CAT at high risk of recurrent events. 45 For example, a correlation between sCLEC-2 (soluble C-type lectin-like receptor 2) levels and podoplanin expression has recently been established in patients with high-grade gliomas.…”

Section: Highlightsmentioning

confidence: 99%

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Updates in the Incidence, Pathogenesis, and Management of Cancer and Venous Thromboembolism

Girardi

Wang

Ageno

et al. 2023

ATVB

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Patients with cancer are at higher risk of developing venous thromboembolism (VTE) compared with the general population. This elevated risk is due to several risk factors and multiple, overlapping thrombotic and hemostatic pathophysiological pathways that are specific to this patient population. Hence, the management of cancer-associated VTE can be challenging for clinicians. Patients with cancer-associated VTE are at higher risk of both recurrent events despite anticoagulation and bleeding complications due to the anticoagulant regimens. Direct oral anticoagulants have recently been shown to be effective, safe, and more convenient than parenteral low-molecular-weight heparin for the management of cancer-associated VTE. Despite these recent advances in anticoagulant therapy, many unmet needs remain in these patients (increased risk of bleeding with specific cancer types, drug-to-drug interactions, liver dysfunction). Factor XI inhibitors are currently being assessed for the management of cancer-associated VTE and may help clinicians address these important knowledge gaps.

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“…When platelets are activated, sCLEC-2 in plasma is measured as a shed form of 25 kD molecule, and 32 kD and 40 kD molecules bound to extracellular vesicles released from the platelets, which was confirmed by ELISA and Western blotting using the same combination of monoclonal antibodies as CLEIA. 1 The relationship between sCLEC-2 and several diseases has been reported in disseminated intravascular coagulation, 4 17 thrombotic microangiopathy, 18 COVID-19, 19 traumatic brain injury, 5 venous thromboembolism 20 and acute coronary syndrome. 2 However, it should be elucidated whether sCLEC-2 can be a predictor of outcomes in these diseases by prospective observational studies.…”

Section: Discussionmentioning

confidence: 99%

Soluble C-type lectin-like receptor 2 in stroke (CLECSTRO) study: protocol of a multicentre, prospective cohort of a novel platelet activation marker in acute ischaemic stroke and transient ischaemic attack

Uchiyama,

Suzuki-Inoue,

Wada

et al. 2023

BMJ Open

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IntroductionSoluble C-type lectin-like receptor 2 (sCLEC-2) is a new biomarker for platelet activation, which can be easily measured by usual blood collection. We conducted the CLECSTRO, a prospective, observational cohort study, to evaluate the clinical implications of sCLEC-2 in patients with acute ischaemic stroke (AIS) and transient ischaemic attack (TIA).Methods and analysisThe participants are patients with AIS/TIA and control patients required for differentiation from AIS/TIA. The target population is 600, including the patients and controls, who would be recruited from eight stroke centres across Japan. The inclusion criteria are AIS within 24 hours of onset and a modified Rankin Scale (mRS) score of 0–2, TIA within 7 days of onset, and contemporary patients required for differentiation from AIS/TIA. Plasma sCLEC-2 will be measured by high-sensitive chemiluminescent enzyme immunoassay using residual blood samples from routine laboratory examinations at the first visit in all patients and 7 days later or at discharge in patients with AIS/TIA. The outcomes include plasma levels of sCLEC-2 in patients with AIS/TIA and controls, sCLEC-2/D-dimer ratio in non-cardioembolic and cardioembolic AIS/TIA, correlation of sCLEC-2 with recurrence or worsening of stroke, severity of stroke, infarct size, ABCD2score in TIA and outcome (mRS) at 7 days and 3 months.Ethics and disseminationThis study was approved by the Ethical Committee of the University of Yamanashi as the central ethical committee in agreement with the ethical committees of all collaborative stroke centres. Informed consent will be obtained by an opt-out form from the patients at each stroke centre according to the Ethical Guidelines for Medical and Biological Research Involving Human Subjects by the Japanese Ministry of Health, Labour and Welfare.Trial registration numbersNCT05579405, UMIN000048954

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Elevated ratio of C-type lectin-like receptor 2 level and platelet count (C2PAC) aids in the diagnosis of post-operative venous thromboembolism in IDH-wildtype gliomas

Cited by 9 publications

References 23 publications

C-Type Lectin-like Receptor 2 Expression Is Decreased upon Platelet Activation and Is Lower in Most Tumor Entities Compared to Healthy Controls

C-Type Lectin-like Receptor 2 Expression Is Decreased upon Platelet Activation and Is Lower in Most Tumor Entities Compared to Healthy Controls

Updates in the Incidence, Pathogenesis, and Management of Cancer and Venous Thromboembolism

Soluble C-type lectin-like receptor 2 in stroke (CLECSTRO) study: protocol of a multicentre, prospective cohort of a novel platelet activation marker in acute ischaemic stroke and transient ischaemic attack

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