Decreased Levels of Histidine-Rich Glycoprotein in Advanced Lung Cancer: Association with Prothrombotic Alterations

Abstract

Background. Histidine-rich glycoprotein (HRG) displays anticoagulant and antifibrinolytic properties in animal models, but its effects in humans are unclear. We investigated serum HRG levels and their associations with the disease stage and prothrombotic alterations in lung cancer (LC) patients. Methods. In 148 patients with advanced LC prior to anticancer therapy (87 non-small-cell LC and 61 small-cell LC) versus 100 well-matched controls, we measured HRG levels in association with clot permeability (Ks), clot turbidimetry (lag phase and maximum absorbance), and clot lysis time (CLT). Results. Compared to controls, LC patients had 45.9% lower HRG levels with no associations with demographics and comorbidities. Decreased HRG, defined as the 90th percentile of control values (<52.7 μg/ml), was 16 times more common in subjects with than without LC (OR=16.4, 95% CI 9.2-23.5, p<0.01). HRG<38 μg/ml discriminated stage IIIAB/limited disease from IV/extensive disease (ED) LC. In LC patients, HRG correlated inversely with CLT (r=−0.41, p<0.001), but not with other fibrin variables. Among stage IV/ED LC, HRG correlated significantly with Ks and lag phase (r=0.28 and r=0.33, respectively, both p<0.001). LC patients with low Ks (10th percentile of control values) combined with prolonged CLT (90th percentile of control values) had reduced HRG levels compared to the remainder (p=0.003). No such observations were noted in controls. Conclusions. Our study is the first to show that decreased HRG levels occur in advanced LC and are associated with the disease stage and hypofibrinolysis.

Plasma proteomic profile associated with platelet dysfunction after trauma

“…Finally, HRG maintains circulating neutrophils in the quiescent state 41 . Though not previously linked to trauma, low plasma levels have been found in multiple disease states, 42–45 and supplementation in rodent models of sepsis and pancreatitis decreases the development of immunothrombosis and improves survival 43,46 . The cause of decreased HRG levels are unknown, but the effect of low HRG is thought to be related to the mitigation of an overwhelming inflammatory response.…”

Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer’s disease

“…LysC (4.5 μg; Wako) was used for overnight digestion at room temperature. Samples were then diluted to 1 M urea with 50 mM ammonium bicarbonate (ABC) ( 68 ). An equal amount (4.5 μg) of trypsin (Promega) was added, and the samples were subsequently incubated for 12 hours.…”

Metabolite, Protein, And Tissue Dysfunction Associated With COVID-19 Disease Severity

“…HRG can also enhance complement activation on necrotic tissues 90 and is directly involved in clearing of apoptotic 91 and necrotic cells [92][93][94] . Low HRG levels have been observed in patients with advanced lung cancer 95 and advanced liver cirrhosis 96 . Therefore, our findings of depleted HRG levels could be indicative of organ damage in the severe COVID-19 patients, similar to what has been observed in other pathologies.…”