Predicting disease progression in advanced non-small cell lung cancer with circulating neutrophil-derived and platelet-derived microparticles

Abstract

Background Microparticles (MPs) are extracellular vesicles that are associated with cancer development and progression. Advanced non-small cell lung cancer (NSCLC) still shows disease progression after multiple lines of treatment. Therefore, the objective of this study was to explore the correlation between circulating MPs and disease progression in advanced NSCLC, and to find a new method for concise and rapid determination of disease progression. Methods Patients with advanced NSCLC admitted to hospital between October 2019 and October 2020 were included and divided into objective remission (OR) and progressive disease (PD) groups. The morphology of MPs was observed using transmission electron microscopy. The circulating total MPs, neutrophil MPs (NMPs), and platelet MPs (PMPs) before and after treatment were detected by flow cytometry, and a predictive model for disease progression in advanced NSCLC was developed. Results Eighty-six patients were included; 60 in the OR group and 26 in the PD group. There was no significant difference in total MPs, NMPs, or PMPs at baseline between the two groups. After treatment, total MPs, NMPs, and PMPs were significantly higher in the PD than those in the OR group. Multivariate regression analysis showed that post-treatment NMPs≥160 events/μL(OR,3.748;95%CI,1.147–12.253,p = 0.029), PMPs≥80 events/μL(OR,10.968;95%CI,2.973–40.462,p < 0.0001) and neutrophil/lymphocyte ratio (NLR) ≥3.3 (OR,4.929;95%CI,1.483–16.375,p = 0.009) were independently associated with progression of advanced NSCLC. Post-treatment NMPs and PMPs combined with NLR were used to build a predictive model for progression of advanced NSCLC. The area under the curve was 0.825 (95%CI,0.715–0.934, p < 0.0001), optimal cut-off value was 16, sensitivity was 80.8%, and specificity was 88.3%. Conclusion NMPs and PMPs are associated with progression of advanced NSCLC. The predictive model for progression of advanced NSCLC, established combining NMPs, PMPs, and NLR, can screen out 80.8% of patients with PD. This is helpful for real-time accurate, concise and rapid assessment of disease progression and timely adjustment of drug therapy. Trial registration Chinese Clinical Trial Registry, ChiCTR1800020223. Registered 20 December 2018, http://www.chictr.org.cn/index.aspx.

The role of platelets in the regulation of tumor growth and metastasis: the mechanisms and targeted therapy

“…176 The transcriptional profile of normal platelets differs from that of platelets isolated from patients with plateletassociated diseases. 177 Based on this evidence, platelets are an attractive platform for cancer diagnosis and prognosis. Specifically, scientists have focused on tumor-educated blood platelets (TEPs) as these platelets changed their F I G U R E 6 Presentation of platelet receptors and intracellular signaling among several kinds of cells.…”

“…The transcriptional profile of normal platelets differs from that of platelets isolated from patients with platelet‐associated diseases 177 . Based on this evidence, platelets are an attractive platform for cancer diagnosis and prognosis.…”

Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer

“…The authors speculated that these increased levels of PMPs (as well as those of other biomarkers) were related to CAT in lung cancer patients [82]. In an even more recent study, Liu et al reported that the circulating levels of both PMPs and neutrophil microparticles (NMPs) were increased in treated, advanced NSCLC patients who had progressive disease, as opposed to those with objective remission [83]. They suggested that combining laboratory indices such as these may predict disease progression in lung cancer [83].…”

Blood Cell-Derived Microvesicles in Hematological Diseases and beyond

“…As previously referred, the linkage of blood cell derived MVs with the pathogenesis of many diseases has suggested their use as disease biomarkers. In the case of NMVs, their accumulation in blood has been strongly associated with disease severity in sepsis [ 28 , 43 , 44 ], in non-small cell lung cancer [ 45 , 46 , 47 ], and in familial hypercholesterolemia, in which they have been suggested as biomarkers of atherosclerotic plaque burden in asymptomatic patients [ 48 ]. Moreover, their levels can be used as an independent biomarker for the prediction of mortality in infectious endocarditis [ 51 ].…”