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Identification of biomarkers for endometriosis using clinical proteomics.

Zhao Y, Liu YN, Li Y, Tian L, Ye X, Cui H, Chang XH - Chin. Med. J. (2015)

Bottom Line: We found a cluster of 5 peptides (4210, 5264, 2660, 5635, and 5904 Da), using 3 peptides (4210, 5904, 2660 Da) to discriminate EM patients from healthy volunteers, with 96.67% sensitivity and 100% specificity.ClinProt can identify EM biomarkers, which - most notably - distinguish even early-stage or minimal disease.We found 5 stable peaks at 4210, 5264, 2660, 5635, and 5904 Da as potential EM biomarkers, the strongest of which were associated with ATP1B4 (4210 Da) and FGA (5904 Da); this indicates that ATP1B4 and FGA are associated with EM pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Gynecology Oncology Center, Peking University People's Hospital, Beijing 100044, China.

ABSTRACT

Background: We investigated possible biomarkers for endometriosis (EM) using the ClinProt technique and proteomics methods.

Methods: We enrolled 50 patients with EM, 34 with benign ovarian neoplasms and 40 healthy volunteers in this study. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) combined with weak cationic exchange (WCX) magnetic beads. Possible biomarkers were analyzed by a random and repeat pattern model-validation method that we designed, and ClinProtools software, results were refined using online liquid chromatography-tandem MS.

Results: We found a cluster of 5 peptides (4210, 5264, 2660, 5635, and 5904 Da), using 3 peptides (4210, 5904, 2660 Da) to discriminate EM patients from healthy volunteers, with 96.67% sensitivity and 100% specificity. We selected 4210 and 5904 m/z, which differed most between patients with EM and controls, and identified them as fragments of ATP1B4, and the fibrinogen alpha (FGA) isoform 1/2 of the FGA chain precursor, respectively.

Conclusions: ClinProt can identify EM biomarkers, which - most notably - distinguish even early-stage or minimal disease. We found 5 stable peaks at 4210, 5264, 2660, 5635, and 5904 Da as potential EM biomarkers, the strongest of which were associated with ATP1B4 (4210 Da) and FGA (5904 Da); this indicates that ATP1B4 and FGA are associated with EM pathogenesis.

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Related in: MedlinePlus

Distribution and performance of serum peptide biomarker for (a) 4210 m/z and (b) 5904 m/z. Receiver operator characteristic of (c) 4210 m/z and (d) 5905 m/z distinguishes patients with endometriosis (EM) from healthy controls. Red: Controls; green: Patients with EM.
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Figure 5: Distribution and performance of serum peptide biomarker for (a) 4210 m/z and (b) 5904 m/z. Receiver operator characteristic of (c) 4210 m/z and (d) 5905 m/z distinguishes patients with endometriosis (EM) from healthy controls. Red: Controls; green: Patients with EM.

Mentions: We collected data for nine samples using an Auto Flex II MALDI-TOF/TOF operated in linear mode for 400 shots to draw peptide mass fingerprints for of 4210, 5904, 5264, 5635, and 2600 m/z [Figure 4]. Of these five peaks, 4210 and 5904 m/z had high discrepancy peaks without interference peaks, which facilitate follow-up peptide identification; whereas peak intensities of 5263, 5635, and 2600 m/z were too low or had intensive interference peaks, which impede follow-up identification. The two selected peaks (4210 m/z, 5904 m/z) also showed the biggest differences between EM patients and controls [Figure 5]. LC-MS/MS showed the amino acid sequence of the 4210 m/z peptide as IMSEYLWDPERRMFLARTGQSWSLILLIYFFFY, a fragment of ATP1B4; and the 5904 m/z peptide sequence as SSSYSKQFTSSTSYNRGDSTFESKSYKMADEAGSE ADHEGTHSTKRGHAKSRPV, which is a fragment of the fibrinogen alpha (FGA) isoform 1/2 of the FGA chain precursor.


Identification of biomarkers for endometriosis using clinical proteomics.

Zhao Y, Liu YN, Li Y, Tian L, Ye X, Cui H, Chang XH - Chin. Med. J. (2015)

Distribution and performance of serum peptide biomarker for (a) 4210 m/z and (b) 5904 m/z. Receiver operator characteristic of (c) 4210 m/z and (d) 5905 m/z distinguishes patients with endometriosis (EM) from healthy controls. Red: Controls; green: Patients with EM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836258&req=5

Figure 5: Distribution and performance of serum peptide biomarker for (a) 4210 m/z and (b) 5904 m/z. Receiver operator characteristic of (c) 4210 m/z and (d) 5905 m/z distinguishes patients with endometriosis (EM) from healthy controls. Red: Controls; green: Patients with EM.
Mentions: We collected data for nine samples using an Auto Flex II MALDI-TOF/TOF operated in linear mode for 400 shots to draw peptide mass fingerprints for of 4210, 5904, 5264, 5635, and 2600 m/z [Figure 4]. Of these five peaks, 4210 and 5904 m/z had high discrepancy peaks without interference peaks, which facilitate follow-up peptide identification; whereas peak intensities of 5263, 5635, and 2600 m/z were too low or had intensive interference peaks, which impede follow-up identification. The two selected peaks (4210 m/z, 5904 m/z) also showed the biggest differences between EM patients and controls [Figure 5]. LC-MS/MS showed the amino acid sequence of the 4210 m/z peptide as IMSEYLWDPERRMFLARTGQSWSLILLIYFFFY, a fragment of ATP1B4; and the 5904 m/z peptide sequence as SSSYSKQFTSSTSYNRGDSTFESKSYKMADEAGSE ADHEGTHSTKRGHAKSRPV, which is a fragment of the fibrinogen alpha (FGA) isoform 1/2 of the FGA chain precursor.

Bottom Line: We found a cluster of 5 peptides (4210, 5264, 2660, 5635, and 5904 Da), using 3 peptides (4210, 5904, 2660 Da) to discriminate EM patients from healthy volunteers, with 96.67% sensitivity and 100% specificity.ClinProt can identify EM biomarkers, which - most notably - distinguish even early-stage or minimal disease.We found 5 stable peaks at 4210, 5264, 2660, 5635, and 5904 Da as potential EM biomarkers, the strongest of which were associated with ATP1B4 (4210 Da) and FGA (5904 Da); this indicates that ATP1B4 and FGA are associated with EM pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Gynecology Oncology Center, Peking University People's Hospital, Beijing 100044, China.

ABSTRACT

Background: We investigated possible biomarkers for endometriosis (EM) using the ClinProt technique and proteomics methods.

Methods: We enrolled 50 patients with EM, 34 with benign ovarian neoplasms and 40 healthy volunteers in this study. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) combined with weak cationic exchange (WCX) magnetic beads. Possible biomarkers were analyzed by a random and repeat pattern model-validation method that we designed, and ClinProtools software, results were refined using online liquid chromatography-tandem MS.

Results: We found a cluster of 5 peptides (4210, 5264, 2660, 5635, and 5904 Da), using 3 peptides (4210, 5904, 2660 Da) to discriminate EM patients from healthy volunteers, with 96.67% sensitivity and 100% specificity. We selected 4210 and 5904 m/z, which differed most between patients with EM and controls, and identified them as fragments of ATP1B4, and the fibrinogen alpha (FGA) isoform 1/2 of the FGA chain precursor, respectively.

Conclusions: ClinProt can identify EM biomarkers, which - most notably - distinguish even early-stage or minimal disease. We found 5 stable peaks at 4210, 5264, 2660, 5635, and 5904 Da as potential EM biomarkers, the strongest of which were associated with ATP1B4 (4210 Da) and FGA (5904 Da); this indicates that ATP1B4 and FGA are associated with EM pathogenesis.

Show MeSH
Related in: MedlinePlus