Prognostic value of circulating markers of neutrophil activation, neutrophil extracellular traps, coagulation and fibrinolysis in patients with terminal cancer

Rosell, Axel; Aguilera, Katherina; Hisada, Yohei; Schmedes, Clare M.; Mackman, Nigel; Wallén, Håkan; Lundström, Staffan; Thålin, Charlotte

doi:10.1038/s41598-021-84476-3

Cited by 28 publications

(19 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasma samples from 50 sex and age matched healthy individuals were obtained from controls included in a previous study investigating NETs in cancer patients 22 . The group comprised of 66% men (n = 33) and the median age was 68 (IQR 56–71).…”

Section: Methodsmentioning

confidence: 99%

Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma

Zenlander

Havervall

Magnusson

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

Neutrophil extracellular traps (NETs) are web-like structures consisting of DNA, histones and granule proteins, released from neutrophils in thrombus formation, inflammation, and cancer. We asked if plasma levels of the NET markers myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit)-DNA, are elevated in liver cirrhosis and hepatocellular carcinoma (HCC) and if the levels correlate with clinical parameters. MPO-DNA, H3Cit-DNA, and thrombin–antithrombin (TAT) complex, as a marker of coagulation activity, were measured using ELISA in plasma from 82 patients with HCC, 95 patients with cirrhosis and 50 healthy controls. Correlations were made to clinical parameters and laboratory data and patients were followed for a median of 22.5 months regarding thrombosis development. H3Cit-DNA was significantly (p < 0.01) elevated in plasma from cirrhosis (66.4 ng/mL) and HCC (63.8 ng/mL) patients compared to healthy controls (31.8 ng/mL). TAT levels showed similar pattern (3.1, 3.7, and 0.0 µg/mL respectively, p < 0.01). MPO-DNA was significantly (p < 0.01) elevated in cirrhosis patients (0.53 O.D.) as compared to controls (0.33 O.D.). Levels of MPO-DNA and H3Cit-DNA correlated positively with Child–Pugh and MELD score. TAT was increased in all Child–Pugh and MELD groups. In multivariable logistic regression, Child B and C liver cirrhosis were independent predictors of elevated H3Cit-DNA in plasma. Levels of MPO-DNA and H3Cit-DNA were similar in patients with or without history of thrombosis, or thrombus formation during follow-up. In conclusion, plasma markers of NET formation are elevated in liver cirrhosis and correlate to the degree of liver dysfunction in patients with liver cirrhosis and/or HCC. The presence of HCC did not further increase the plasma levels of NET markers as compared to patients with cirrhosis only.

show abstract

Section: Methodsmentioning

confidence: 99%

Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma

Zenlander

Havervall

Magnusson

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, the correlations between NETs and coagulation/fibrinolysis markers were weak or non-existing. This observation suggests that NETs contribute to poor prognosis in terminal cancer through mechanisms independent of thrombosis [31]. Consistently Oklu et al [29] detected high levels of nucleosomes, cfDNA, DNase-1, the thrombin-antithrombin III (TAT) complex, as well as endonuclease-G and its activity in plasma from cancer patients.…”

Section: Circulating Net Markers In Cancer Patientsmentioning

confidence: 66%

Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis

Demkow

2021

Cancers

123

View full text Add to dashboard Cite

The present review highlights the complex interactions between cancer and neutrophil extracellular traps (NETs). Neutrophils constitute the first line of defense against foreign invaders using major effector mechanisms: phagocytosis, degranulation, and NETs formation. NETs are composed from decondensed nuclear or mitochondrial DNA decorated with proteases and various inflammatory mediators. Although NETs play a crucial role in defense against systemic infections, they also participate in non-infectious conditions, such as inflammation, autoimmune disorders, and cancer. Cancer cells recruit neutrophils (tumor-associated neutrophils, TANs), releasing NETs to the tumor microenvironment. NETs were found in various samples of human and animal tumors, such as pancreatic, breast, liver, and gastric cancers and around metastatic tumors. The role of the NETs in tumor development increasingly includes cancer immunoediting and interactions between the immune system and cancer cells. According to the accumulated evidence, NETs awake dormant cancer cells, causing tumor relapse, as well as its unconstrained growth and spread. NETs play a key regulatory role in the tumor microenvironment, such as the development of distant metastases through the secretion of proteases, i.e., matrix metalloproteinases and proinflammatory cytokines. NETs, furthermore, directly exacerbate tumor aggressiveness by enhancing cancer migration and invasion capacity. The collected evidence also states that through the induction of the high-mobility group box 1, NETs induce the epithelial to mesenchymal transition in tumor cells and, thereby, potentiate their invasiveness. NET proteinases can also degrade the extracellular matrix, promoting cancer cell extravasation. Moreover, NETs can entrap circulating cancer cells and, in that way, facilitate metastasis. NETs directly trigger tumor cell proliferation through their proteases or activating signals. This review focused on the pro-tumorigenic action of NETs, in spite of its potential to also exhibit an antitumor effect. NET components, such as myeloperoxidase or histones, have been shown to directly kill cancer cells. A better understanding of the crosstalk between cancer and NETs can help to devise novel approaches to the therapeutic interventions that block cancer evasion mechanisms and prevent metastatic spread. This review sought to provide the most recent knowledge on the crosstalk between NETs and cancer, and bring more profound ideas for future scientists exploring this field.

show abstract

“…92 The role of NETs in predicting cancer outcomes was evaluated in 106 terminal cancer patients. 97 The results show that neutrophil activation and NET markers, but not markers of coagulation and fibrinolysis, are strongly associated with poor prognosis, 97 suggesting that neutrophils and NETs contribute to a poor prognosis through pathways not directly related to coagulation.…”

Section: Neutrophil Extracellular Trapsmentioning

confidence: 99%

Hemostatic Biomarkers and Cancer Prognosis: Where Do We Stand?

Falanga

Marchetti

Russo

2021

Semin Thromb Hemost

View full text Add to dashboard Cite

Cancer patients are characterized by hypercoagulable state and an increased rate of thrombotic events, the most common being venous thromboembolism. Several hemostatic pathways that are significantly implicated in mechanisms of thromboembolic disease are also involved in growth, invasion, and metastatic spread of malignant cells as well in tumor-induced neo-angiogenesis. This close connection between cancer and the hemostatic system has prompted numerous studies on the role of alterations in the level plasma biomarkers of the different compartments of hemostasis in predicting cancer prognosis. In this review, we collect the results of several exemplificative studies that have evaluated clotting activation biomarkers in relation to different cancer outcomes with a final emphasis on current research and forthcoming directions in this field.

show abstract

Prognostic value of circulating markers of neutrophil activation, neutrophil extracellular traps, coagulation and fibrinolysis in patients with terminal cancer

Cited by 28 publications

References 70 publications

Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma

Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma

Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis

Hemostatic Biomarkers and Cancer Prognosis: Where Do We Stand?

Contact Info

Product

Resources

About