Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of quiescin Q6 as a candidate biomarker of acutely decompensated heart failure.
OBJECTIVE
Biochemical marker testing has improved the evaluation and management of patients with cardiovascular diseases over the past decade. Natriuretic peptides (NPs), used in clinical practice to assess cardiac dysfunction, exhibit many limitations, however. We used an unbiased proteomics approach for the discovery of novel diagnostic plasma biomarkers of heart failure (HF).


RESULTS
A proteomics pipeline adapted for very low-abundant plasma proteins was applied to clinical samples from patients admitted with acute decompensated HF (ADHF). Quiescin Q6 (QSOX1), a protein involved in the formation of disulfide bridges, emerged as the best performing marker for ADHF (with an area under the receiver operator characteristic curve of 0.86, 95% confidence interval: 0.79-0.92), and novel isoforms of NPs were also identified. Diagnostic performance of QSOX1 for ADHF was confirmed in 267 prospectively collected subjects of whom 76 had ADHF. Combining QSOX1 to B-type NP (BNP) significantly improved diagnostic accuracy for ADHF by particularly improving specificity. Using thoracic aortic constriction in rats, QSOX1 was specifically induced within both left atria and ventricles at the time of HF onset.


CONCLUSIONS
The novel biomarker QSOX1 accurately identifies ADHF, particularly when combined with BNP. Through both clinical and experimental studies we provide lines of evidence for a link between ADHF and cardiovascular production of QSOX1.
Department of Anesthesia and Intensive Care, U942 Inserm, Paris Diderot University, Lariboisière Hospital, 2 rue Ambroise Paré, 75010 Paris, France. alexandre.mebazaa@lrb.aphp.fr
Alexandre
A
Mebazaa
Griet
G
Vanpoucke
Gregoire
G
Thomas
Katleen
K
Verleysen
Alain
A
Cohen-Solal
Marc
M
Vanderheyden
Jozef
J
Bartunek
Christian
C
Mueller
Jean-Marie
JM
Launay
Natalie
N
Van Landuyt
Filip
F
D'Hondt
Elisabeth
E
Verschuere
Caroline
C
Vanhaute
Robin
R
Tuytten
Lies
L
Vanneste
Koen
K
De Cremer
Jan
J
Wuyts
Huw
H
Davies
Piet
P
Moerman
Damien
D
Logeart
Corinne
C
Collet
Brice
B
Lortat-Jacob
Miguel
M
Tavares
Wouter
W
Laroy
James L
JL
Januzzi
Jane-Lise
JL
Samuel
Koen
K
Kas
D000368:Aged; D000818:Animals; D001013:Aorta, Thoracic; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003250:Constriction; D004417:Dyspnea / Q000209:etiology; D005260:Female; D006333:Heart Failure / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000097:blood*; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D051381:Rats
D015415:Biomarkers; D050862:Oxidoreductases Acting on Sulfur Group Donors; C117183:QSOX1 protein, human