Sets of serum exosomal microRNAs as candidate diagnostic biomarkers for Kawasaki disease.
Although Kawasaki disease is the main cause of acquired heart disease in children, no diagnostic biomarkers are available. We aimed to identify candidate biomarkers for diagnosing Kawasaki disease using serum exosomal microRNAs (miRNAs). Using frozen serum samples from a biobank, high-throughput microarray technologies, two-stage real-time quantitative PCR, and a self-referencing strategy for data normalization, we narrowed down the list of biomarker candidates to a set of 4 miRNAs. We further validated the diagnostic capabilities of the identified miRNAs (namely, CT(miR-1246)-CT(miR-4436b-5p) and CT(miR-197-3p)-CT(miR-671-5p)) in 79 samples from two hospitals. We found that this 4-miRNA set could distinguish KD patients from other febrile patients as well as from healthy individuals in a single pass, with a minimal rate of false positives and negatives. We thus propose, for the first time, that serum exosomal miRNAs represent candidate diagnostic biomarkers for Kawasaki disease. Additionally, we describe an effective strategy of screening for biomarkers of complex diseases even when little mechanistic knowledge is available.
Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China.
Hong-Ling
HL
Jia
State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070, Guangdong, China.
Chao-Wu
CW
Liu
Guangzhou Women and Children's Medical Center, Guangzhou 510120, Guangdong, China.
Li
L
Zhang
Information Center, Shenzhen Children's Hospital, Shenzhen, 518038, Guangdong, China.
Wei-Jun
WJ
Xu
Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China.
Xue-Juan
XJ
Gao
Foshan Women and Children's Hospital, Foshan, 528000, Guangdong, China.
Jun
J
Bai
Guangzhou Women and Children's Medical Center, Guangzhou 510120, Guangdong, China.
Yu-Fen
YF
Xu
Department of Pediatric Cardiology, Shenzhen Children's Hospital, Shenzhen, 518038, Guangdong, China.
Ming-Guo
MG
Xu
Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China.
Gong
G
Zhang
D015415:Biomarkers / Q000097:blood; D055354:Exosomes / Q000235:genetics* / Q000648:ultrastructure; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D012015:Reference Standards; D015203:Reproducibility of Results
D015415:Biomarkers; D035683:MicroRNAs