Presentation Information
[C14-04]Prediction of therapy responses in Kawasaki disease by the expression of microRNA in endothelial extracellular vesicles.
*Akane Hara1, Hideyuki Nakaoka2, Kaori Tsuboi2, Mako Okabe2, Keijiro Ibuki2, Sayaka Ozawa2, Keiichi Hirono2 (1. Grad. Sch. Med. & Pharm. Sci., Univ. Toyama (Japan), 2. Dept. Pediatr., Fac. Med., Univ. Toyama (Japan))
Keywords:
inflammatory diseases,non-coding RNA,treatment outcome predictor,data analysis
Kawasaki Disease (KD) is an inflammatory disease in young children characterized by blood vessel inflammation throughout the body. About 17 percent of patients do not respond to intravenous immunoglobulin (IVIG), the first-line treatment for KD, and some of them result in severe symptoms such as coronary artery lesions (CAL). The previous clinical study revealed that endothelial extracellular vesicles (EV) are involved in acute KD, and particularly, two specific microRNAs encapsulated in EVs were associated with CAL development1. In this study, we aimed to elucidate microRNA expression profile that will be useful to distinguish IVIG responders from non-responders in acute phase of KD.
We analyzed microRNA expression of IVIG responders, non-responders including CAL patients, and the controls who were not KD patients. The microRNAs were extracted with EVs from the serum samples fractionated by centrifugation and the microarray data was profiled. First, PLS-DA was performed to visualize the variation in microRNA expression among the groups corresponding to the different IVIG responses. VIP score was also calculated to specify the relatively important microRNAs to divide the samples into the groups. Second, random forest was also performed to critical microRNAs to classify the IVIG responses. The microRNAs specified as the important features to divide into the groups by both two analyses were suggested to be useful for IVIG response prediction. We finally performed logistic regression using the specified microRNAs as explanatory variables to predict the IVIG responses. The responders and non-responders were successfully classified within our dataset by the score based on microRNA expression profile, suggesting that the set of microRNAs are associated with acute KD development.
The specified microRNAs are expected to be candidates of biomarkers. They will also provide information about the KD mechanisms when their roles in the regulation of immunity and other systems are examined in detail. In the future, this framework will realize the early diagnosis of refractory KD before starting the therapy, which will change the current strategy into the precision medicine based on the individual microRNA profiles.
Reference:
1. Nakaoka et al. (2018). MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease. Scientific Reports, 8, 1016.
We analyzed microRNA expression of IVIG responders, non-responders including CAL patients, and the controls who were not KD patients. The microRNAs were extracted with EVs from the serum samples fractionated by centrifugation and the microarray data was profiled. First, PLS-DA was performed to visualize the variation in microRNA expression among the groups corresponding to the different IVIG responses. VIP score was also calculated to specify the relatively important microRNAs to divide the samples into the groups. Second, random forest was also performed to critical microRNAs to classify the IVIG responses. The microRNAs specified as the important features to divide into the groups by both two analyses were suggested to be useful for IVIG response prediction. We finally performed logistic regression using the specified microRNAs as explanatory variables to predict the IVIG responses. The responders and non-responders were successfully classified within our dataset by the score based on microRNA expression profile, suggesting that the set of microRNAs are associated with acute KD development.
The specified microRNAs are expected to be candidates of biomarkers. They will also provide information about the KD mechanisms when their roles in the regulation of immunity and other systems are examined in detail. In the future, this framework will realize the early diagnosis of refractory KD before starting the therapy, which will change the current strategy into the precision medicine based on the individual microRNA profiles.
Reference:
1. Nakaoka et al. (2018). MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease. Scientific Reports, 8, 1016.