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Deciphering the ovarian cancer ascites fluid peptidome.

Bery A, Leung F, Smith CR, Diamandis EP, Kulasingam V - Clin Proteomics (2014)

Bottom Line: The resultant fractions were analyzed using an Orbitrap mass spectrometer.We identified over 2000 unique endogenous peptides derived from 259 proteins.Our list of peptides found in ovarian cancer specimens includes fragments derived from the proteins vitronectin, transketolase and haptoglobin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. vathany.kulasingam@uhn.ca.

ABSTRACT

Background: Conventional proteomic approaches have thus far been unable to identify novel serum biomarkers for ovarian cancer that are more sensitive and specific than the current clinically used marker, CA-125. Because endogenous peptides are smaller and may enter the circulation more easily than proteins, a focus on the low-molecular-weight region may reveal novel biomarkers with enhanced sensitivity and specificity. In this study, we deciphered the peptidome of ascites fluid from 3 ovarian cancer patients and 3 benign individuals (ascites fluid from patients with liver cirrhosis).

Results: Following ultrafiltration of the ascites fluids to remove larger proteins, each filtrate was subjected to solid phase extraction and fractionated using strong cation exchange chromatography. The resultant fractions were analyzed using an Orbitrap mass spectrometer. We identified over 2000 unique endogenous peptides derived from 259 proteins. We then catalogued over 777 peptides that were found only in ovarian cancer ascites. Our list of peptides found in ovarian cancer specimens includes fragments derived from the proteins vitronectin, transketolase and haptoglobin.

Conclusions: Peptidomics may uncover previously undiscovered disease-specific endogenous peptides that warrant further investigation as biomarkers for ovarian cancer.

No MeSH data available.


Related in: MedlinePlus

Peptides identified from haptoglobin. A schematic representation of the haptoglobin protein. The highlighted areas reveal the peptides identified per sample. No peptides were identified in the benign samples.
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Figure 4: Peptides identified from haptoglobin. A schematic representation of the haptoglobin protein. The highlighted areas reveal the peptides identified per sample. No peptides were identified in the benign samples.

Mentions: Haptoglobin is a high-abundance serum protein, and has been extensively studied for use as an OvCa marker [33,34], but has never before been studied at the peptide level. In this study, peptides originating from haptoglobin were found exclusively in the three ovarian cancer samples. We identified 47 such peptides in total. Figure 4 displays a schematic representation of identified peptides from the haptoglobin protein in the three OvCa samples, shaded to highlight identified peptide sequences along the length of the entire protein. We noticed that there were five conserved sequences common to at least two of the OvCa samples. Peptides sharing this common “protein core” may have diagnostic utility and merit further investigation. No peptides from haptoglobin were identified in the three benign samples.


Deciphering the ovarian cancer ascites fluid peptidome.

Bery A, Leung F, Smith CR, Diamandis EP, Kulasingam V - Clin Proteomics (2014)

Peptides identified from haptoglobin. A schematic representation of the haptoglobin protein. The highlighted areas reveal the peptides identified per sample. No peptides were identified in the benign samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230032&req=5

Figure 4: Peptides identified from haptoglobin. A schematic representation of the haptoglobin protein. The highlighted areas reveal the peptides identified per sample. No peptides were identified in the benign samples.
Mentions: Haptoglobin is a high-abundance serum protein, and has been extensively studied for use as an OvCa marker [33,34], but has never before been studied at the peptide level. In this study, peptides originating from haptoglobin were found exclusively in the three ovarian cancer samples. We identified 47 such peptides in total. Figure 4 displays a schematic representation of identified peptides from the haptoglobin protein in the three OvCa samples, shaded to highlight identified peptide sequences along the length of the entire protein. We noticed that there were five conserved sequences common to at least two of the OvCa samples. Peptides sharing this common “protein core” may have diagnostic utility and merit further investigation. No peptides from haptoglobin were identified in the three benign samples.

Bottom Line: The resultant fractions were analyzed using an Orbitrap mass spectrometer.We identified over 2000 unique endogenous peptides derived from 259 proteins.Our list of peptides found in ovarian cancer specimens includes fragments derived from the proteins vitronectin, transketolase and haptoglobin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. vathany.kulasingam@uhn.ca.

ABSTRACT

Background: Conventional proteomic approaches have thus far been unable to identify novel serum biomarkers for ovarian cancer that are more sensitive and specific than the current clinically used marker, CA-125. Because endogenous peptides are smaller and may enter the circulation more easily than proteins, a focus on the low-molecular-weight region may reveal novel biomarkers with enhanced sensitivity and specificity. In this study, we deciphered the peptidome of ascites fluid from 3 ovarian cancer patients and 3 benign individuals (ascites fluid from patients with liver cirrhosis).

Results: Following ultrafiltration of the ascites fluids to remove larger proteins, each filtrate was subjected to solid phase extraction and fractionated using strong cation exchange chromatography. The resultant fractions were analyzed using an Orbitrap mass spectrometer. We identified over 2000 unique endogenous peptides derived from 259 proteins. We then catalogued over 777 peptides that were found only in ovarian cancer ascites. Our list of peptides found in ovarian cancer specimens includes fragments derived from the proteins vitronectin, transketolase and haptoglobin.

Conclusions: Peptidomics may uncover previously undiscovered disease-specific endogenous peptides that warrant further investigation as biomarkers for ovarian cancer.

No MeSH data available.


Related in: MedlinePlus