PAI‐1 and protein C as early markers of veno‐occlusive disease in patients treated for Wilms tumor

Abstract

Background Hepatic veno‐occlusive (VOD) disease has been described in hematopoietic stem cell transplantation (HSCT), solid tumors, and acute lymphoblastic leukemia. The incidence of VOD in Wilms tumor (WT) ranges from 1.2% to 8%. The diagnosis of VOD is clinical, and there are no validated laboratory biomarkers. Procedure We prospectively evaluated the specificity and sensitivity of plasminogen‐activator inhibitor‐1 (PAI‐1) and protein C as diagnostic markers of VOD in WT patients. Fifty patients treated from 2008 to 2016 for WT were eligible. VOD was diagnosed according to modified Seattle criteria and retrospectively reclassified according to the recently published criteria for VOD in pediatric HSCT patients. Results VOD occurred in 6 of 50 patients (12%) after 20 to 97 days from starting chemotherapy. The average duration of VOD was 10 days (range, 4–13 days). PAI‐1 levels were elevated in all VOD patients, while a decrease in protein C levels was observed in 33% of patients with VOD. PAI‐1 antigen (Ag) values ≥ 26.4 ng/mL demonstrated high sensitivity and specificity for the clinical diagnosis of VOD with sensitivity 100%, specificity 93%; whereas protein C levels below 34.5% had sensitivity 67%, specificity 100%. Both PAI‐1 and protein C had an high negative predictive value: PAI‐1 Ag 100%; protein C 95%. Conclusions PAI‐1 Ag and protein C have good sensitivity and specificity for the diagnosis of VOD in WT patients. Their high negative predictive value can be used in the differential diagnosis of liver toxicity, especially in VOD episodes with absent or delayed hyperbilirubinemia.

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor

“…The current treatment for children with Wilms tumor includes chemotherapy, which is given before or after surgery. Despite the increased cure rate for Wilms tumor following multimodal therapy, the recurrence rate remained relatively high (15%) for patients with low-grade Wilms tumor, and the five-year survival rate remains poor [23][24][25][26]. Therefore, an increasing number of studies have included the search for drugs to target the relevant genes in Wilms tumor, and have included salidroside and curcumin [27,28].…”