The plasma peptides of breast versus ovarian cancer.

Breast cancer Chi Square test and ANOVA Discovery of variation Electrospray ionization tandem mass spectrometry Human EDTA plasma LC–ESI–MS/MS Linear quadrupole ion trap Nano chromatography Organic extraction Random and independent sampling SQL SERVER and R

Journal

Clinical proteomics
ISSN: 1542-6416
Titre abrégé: Clin Proteomics
Pays: England
ID NLM: 101184586

Informations de publication

Date de publication:
2019
Historique:
received: 02 08 2019
accepted: 05 12 2019
entrez: 1 1 2020
pubmed: 1 1 2020
medline: 1 1 2020
Statut: epublish

Résumé

There is a need to demonstrate a proof of principle that proteomics has the capacity to analyze plasma from breast cancer versus other diseases and controls in a multisite clinical trial design. The peptides or proteins that show a high observation frequency, and/or precursor intensity, specific to breast cancer plasma might be discovered by comparison to other diseases and matched controls. The endogenous tryptic peptides of breast cancer plasma were compared to ovarian cancer, female normal, sepsis, heart attack, Alzheimer's and multiple sclerosis along with the institution-matched normal and control samples collected directly onto ice. Endogenous tryptic peptides were extracted from individual breast cancer and control EDTA plasma samples in a step gradient of acetonitrile, and collected over preparative C18 for LC-ESI-MS/MS with a set of LTQ XL linear quadrupole ion traps working together in parallel to randomly and independently sample clinical populations. The MS/MS spectra were fit to fully tryptic peptides or phosphopeptides within proteins using the X!TANDEM algorithm. The protein observation frequency was counted using the SEQUEST algorithm after selecting the single best charge state and peptide sequence for each MS/MS spectra. The observation frequency was subsequently tested by Chi Square analysis. The log Peptides and/or phosphopeptides of common plasma proteins such as APOE, C4A, C4B, C3, APOA1, APOC2, APOC4, ITIH3 and ITIH4 showed increased observation frequency and/or precursor intensity in breast cancer. Many cellular proteins also showed large changes in frequency by Chi Square (χ There was striking agreement between the breast cancer plasma peptides and proteins discovered by LC-ESI-MS/MS with previous biomarkers from tumors, cells lines or body fluids by genetic or biochemical methods. The results indicate that variation in plasma peptides from breast cancer versus ovarian cancer may be directly discovered by LC-ESI-MS/MS that will be a powerful tool for clinical research. It may be possible to use a battery of sensitive and robust linear quadrupole ion traps for random and independent sampling of plasma from a multisite clinical trial.

Sections du résumé

BACKGROUND BACKGROUND
There is a need to demonstrate a proof of principle that proteomics has the capacity to analyze plasma from breast cancer versus other diseases and controls in a multisite clinical trial design. The peptides or proteins that show a high observation frequency, and/or precursor intensity, specific to breast cancer plasma might be discovered by comparison to other diseases and matched controls. The endogenous tryptic peptides of breast cancer plasma were compared to ovarian cancer, female normal, sepsis, heart attack, Alzheimer's and multiple sclerosis along with the institution-matched normal and control samples collected directly onto ice.
METHODS METHODS
Endogenous tryptic peptides were extracted from individual breast cancer and control EDTA plasma samples in a step gradient of acetonitrile, and collected over preparative C18 for LC-ESI-MS/MS with a set of LTQ XL linear quadrupole ion traps working together in parallel to randomly and independently sample clinical populations. The MS/MS spectra were fit to fully tryptic peptides or phosphopeptides within proteins using the X!TANDEM algorithm. The protein observation frequency was counted using the SEQUEST algorithm after selecting the single best charge state and peptide sequence for each MS/MS spectra. The observation frequency was subsequently tested by Chi Square analysis. The log
RESULTS RESULTS
Peptides and/or phosphopeptides of common plasma proteins such as APOE, C4A, C4B, C3, APOA1, APOC2, APOC4, ITIH3 and ITIH4 showed increased observation frequency and/or precursor intensity in breast cancer. Many cellular proteins also showed large changes in frequency by Chi Square (χ
CONCLUSION CONCLUSIONS
There was striking agreement between the breast cancer plasma peptides and proteins discovered by LC-ESI-MS/MS with previous biomarkers from tumors, cells lines or body fluids by genetic or biochemical methods. The results indicate that variation in plasma peptides from breast cancer versus ovarian cancer may be directly discovered by LC-ESI-MS/MS that will be a powerful tool for clinical research. It may be possible to use a battery of sensitive and robust linear quadrupole ion traps for random and independent sampling of plasma from a multisite clinical trial.

Identifiants

pubmed: 31889940
doi: 10.1186/s12014-019-9262-0
pii: 9262
pmc: PMC6927194
doi:

Types de publication

Journal Article

Langues

eng

Pagination

43

Informations de copyright

© The Author(s) 2019.

Déclaration de conflit d'intérêts

Competing interestsThe authors declare that they have no competing interests.

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Auteurs

Jaimie Dufresne (J)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Pete Bowden (P)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Thanusi Thavarajah (T)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Angelique Florentinus-Mefailoski (A)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Zhuo Zhen Chen (ZZ)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Monika Tucholska (M)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Tenzin Norzin (T)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Margaret Truc Ho (MT)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Morla Phan (M)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Nargiz Mohamed (N)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.

Amir Ravandi (A)

2Institute of Cardiovascular Sciences, St. Boniface Hospital Research Center, University of Manitoba, Winnipeg, Canada.

Eric Stanton (E)

3Division of Cardiology, Department of Medicine, McMaster University, Hamilton, Canada.

Arthur S Slutsky (AS)

4St. Michael's Hospital, Keenan Chair in Medicine, Professor of Medicine, Surgery & Biomedical Engineering, University of Toronto, Toronto, Canada.

Claudia C Dos Santos (CC)

5St. Michael's Hospital, Keenan Research Centre for Biomedical Science, Toronto, Canada.

Alexander Romaschin (A)

5St. Michael's Hospital, Keenan Research Centre for Biomedical Science, Toronto, Canada.

John C Marshall (JC)

5St. Michael's Hospital, Keenan Research Centre for Biomedical Science, Toronto, Canada.

Christina Addison (C)

6Program for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada.

Shawn Malone (S)

6Program for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada.

Daren Heyland (D)

7Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Canada.

Philip Scheltens (P)

8Alzheimer Center, Dept of Neurology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam Neuroscience, Amsterdam, The Netherlands.

Joep Killestein (J)

9MS Center, Dept of Neurology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam Neuroscience, Amsterdam, The Netherlands.

Charlotte Teunissen (C)

10Neurochemistry Lab and Biobank, Dept of Clinical Chemsitry, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam Neuroscience, Amsterdam, The Netherlands.

Eleftherios P Diamandis (EP)

11Mount Sinai Hospital Research Institute, University of Toronto, Toronto, Canada.

K W M Siu (KWM)

12University of Windsor, Windsor, Canada.

John G Marshall (JG)

1Ryerson Analytical Biochemistry Laboratory (RABL), Department of Chemistry and Biology, Faculty of Science, Ryerson University, 350 Victoria St., Toronto, ON Canada.
13International Biobank of Luxembourg (IBBL), Luxembourg Institute of Health (formerly CRP Sante Luxembourg), Strassen, Luxembourg.

Classifications MeSH