Discovery and validation of urine markers of acute pediatric appendicitis using high-accuracy mass spectrometry.
OBJECTIVE
Molecular definition of disease has been changing all aspects of medical practice, from diagnosis and screening to understanding and treatment. Acute appendicitis is among many human conditions that are complicated by the heterogeneity of clinical presentation and shortage of diagnostic markers. Here, we sought to profile the urine of patients with appendicitis, with the goal of identifying new diagnostic markers.


METHODS
Candidate markers were identified from the urine of children with histologically proven appendicitis by using high-accuracy mass spectrometry proteome profiling. These systemic and local markers were used to assess the probability of appendicitis in a blinded, prospective study of children being evaluated for acute abdominal pain in our emergency department. Tests of performance of the markers were evaluated against the pathologic diagnosis and histologic grade of appendicitis.


RESULTS
Test performance of 57 identified candidate markers was studied in 67 patients, with median age of 11 years, 37% of whom had appendicitis. Several exhibited favorable diagnostic performance, including calgranulin A (S100-A8), alpha-1-acid glycoprotein 1 (orosomucoid), and leucine-rich alpha-2-glycoprotein (LRG), with the receiver operating characteristic area under the curve and values of 0.84 (95% confidence interval [CI] 0.72 to 0.95), 0.84 (95% CI 0.72 to 0.95), and 0.97 (95% CI 0.93 to 1.0), respectively. LRG was enriched in diseased appendices, and its abundance correlated with severity of appendicitis.


CONCLUSIONS
High-accuracy mass spectrometry urine proteome profiling allowed identification of diagnostic markers of acute appendicitis. Usage of LRG and other identified biomarkers may improve the diagnostic accuracy of clinical evaluations of appendicitis.
Kentsis
Alex
A
Division of Emergency Medicine, Department of Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
Lin
Yin Yin
YY
Kurek
Kyle
K
Calicchio
Monica
M
Wang
Yan Yan
YY
Monigatti
Flavio
F
Campagne
Fabien
F
Lee
Richard
R
Horwitz
Bruce
B
Steen
Hanno
H
Bachur
Richard
R
D001064:Appendicitis / Q000175:diagnosis / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D040081:Protein Array Analysis; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index
D015415:Biomarkers