Circulating Endothelial-Derived Activated Microparticle: A Useful Biomarker for Predicting One-Year Mortality in Patients with Advanced Non-Small Cell Lung Cancer

Abstract

Background. This study tested the hypothesis that circulating microparticles (MPs) are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer (ES-NSCLC). Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1) platelet-derived activated MPs (PDAc-MPs), (2) platelet-derived apoptotic MPs (PDAp-MPs), (3) endothelial-derived activated MPs (EDAc-MPs), and (4) endothelial-derived apoptotic MPs (EDAp-MPs), were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1 (n = 56) (one-year survivors) and patients who survived less than one year were categorized into group 2 (n = 51) (one-year nonsurvivors). Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (all P < 0.05). Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1 (P = 0.006). Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (all P < 0.035). Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.

Cell-derived microparticles and the lung

“…Discordant results emerged from another study conducted in 107 end-stage nonsmall cell lung cancer patients, divided into 1-year survivors and nonsurvivors, measuring PMPs and EMPs [60]. While there was no difference in PMPs and "apoptotic" EMPs (defined as CD31 + CD42b − annexinV + microparticles) between the two groups, "activated" EMP levels (defined as CD31 + CD42b − annexinV − microparticles) were significantly higher in nonsurvivors [60]. After a multivariate regression analysis, these higher levels were an independent predictor of 1-year mortality.…”

“…FLEITAS et al [59] found higher levels of total circulating microparticles in 60 patients with nonsmall cell lung cancer compared with 60 controls, but the most relevant finding was that, in cancer patients, higher baseline levels of microparticles were associated with a better progression-free and overall survival. Discordant results emerged from another study conducted in 107 end-stage nonsmall cell lung cancer patients, divided into 1-year survivors and nonsurvivors, measuring PMPs and EMPs [60]. While there was no difference in PMPs and "apoptotic" EMPs (defined as CD31 + CD42b − annexinV + microparticles) between the two groups, "activated" EMP levels (defined as CD31 + CD42b − annexinV − microparticles) were significantly higher in nonsurvivors [60].…”

Extracellular vesicles such as prostate cancer cell fragments as a fluid biopsy for prostate cancer

“…SEM also has significant drawbacks related to preparation of sample(s), with purified EVs inconsistently being immobilized onto the substrate (silica wafers or mica) for SEM imaging. 60 Atomic force microscopy is another valuable tool that enables the determination of ultrastructure for all entities (EVs, plasma proteins) at an atomic resolution. 48 Most recently, this technique was used to understand the ultrastructure of purified platelet MPs 48 and is the only instrument that offers information regarding protein contamination in purified EV fraction owing to its atomic level of resolution.…”

“…The term 'platelet dust' was later replaced with 'microparticles' 57 and 'exosomes', 58 in which platelet MPs are membrane-derived and exosomes being the exocytosed storage granules (alphagranules, dense granules) of platelets. EVs, either MPs or exosomes, are secreted by platelets, 59 endothelial cells 60 and leukocytes, 61 and these types of cell fragments are relatively abundant in different bodily fluids. 2 Through quantification of all circulating MPs in vivo, it is now understood that platelet EVs are the most abundant types of EVs, when compared with MPs from other circulating cells.…”

Endothelial Derived Micro Particles: Biomarkers for Heart Failure Diagnosis and Management

“…Although elevated level of apoptotic EMPs have demonstrated high predictive value for CHF development and clinical outcomes [21][22][23][24], the role of activated EMPs is still not clear. Probably CHF development is the result of both disease-specific and traditional cardiovascular risk factors contributed an imbalance between apoptotic-derived EMPs and activated EMPs forming impaired phenotype.…”