The plasma peptides of ovarian cancer

• Published in: Clinical proteomics 2018-12, Vol.15 (1), p.41-41, Article 41
• Main Authors: Dufresne, Jaimie, Bowden, Pete, Thavarajah, Thanusi, Florentinus-Mefailoski, Angelique, Chen, Zhuo Zhen, Tucholska, Monika, Norzin, Tenzin, Ho, Margaret Truc, Phan, Morla, Mohamed, Nargiz, Ravandi, Amir, Stanton, Eric, Slutsky, Arthur S, Dos Santos, Claudia C, Romaschin, Alexander, Marshall, John C, Addison, Christina, Malone, Shawn, Heyland, Daren, Scheltens, Philip, Killestein, Joep, Teunissen, Charlotte E, Diamandis, Eleftherios P, Michael Siu, K W, Marshall, John G
• Format: Article
• Language: English
• Subjects: Algorithms; Biomarkers; Breast cancer; Centrifugation; Chi-square test; Chromatography; Comparative analysis; Confederate symbols; Electrospray ionization tandem mass spectrometry; Gene expression; Health aspects; High-performance liquid chromatography; Human EDTA plasma; Ionization; Ions; LC–ESI–MS/MS; Leukemia; Linear quadrupole ion trap; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Melanoma; Nano chromatography; Organic extraction; Ovarian cancer; Peptides; Plasma proteins; Proteins; Scientific imaging; Servers; SIRT1 protein; Statistical analysis; Structure-function relationships; Transient receptor potential proteins; Tryptic peptides; Tumors; Variance analysis
• ISSN: 1542-6416; 1559-0275
• DOI: 10.1186/s12014-018-9215-z

It may be possible to discover new diagnostic or therapeutic peptides or proteins from blood plasma by using liquid chromatography and tandem mass spectrometry to identify, quantify and compare the peptides cleaved ex vivo from different clinical populations. The endogenous tryptic peptides of ovarian cancer plasma were compared to breast cancer and female cancer normal controls, other diseases with their matched or normal controls, plus ice cold plasma to control for pre-analytical variation. The endogenous tryptic peptides or tryptic phospho peptides (i.e. without exogenous digestion) were analyzed from 200 μl of EDTA plasma. The plasma peptides were extracted by a step gradient of organic/water with differential centrifugation, dried, and collected over C18 for analytical HPLC nano electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS) with a linear quadrupole ion trap. The endogenous peptides of ovarian cancer were compared to multiple disease and normal samples from different institutions alongside ice cold controls. Peptides were randomly and independently sampled by LC-ESI-MS/MS. Precursor ions from peptides > E4 counts were identified by the SEQUEST and X!TANDEM algorithms, filtered in SQL Server, before testing of frequency counts by Chi Square (χ ), for analysis with the STRING algorithm, and comparison of precursor intensity by ANOVA in the R statistical system with the Tukey-Kramer Honestly Significant Difference (HSD) test. Peptides and/or phosphopeptides of common plasma proteins such as HPR, HP, HPX, and SERPINA1 showed increased observation frequency and/or precursor intensity in ovarian cancer. Many cellular proteins showed large changes in frequency by Chi Square (χ  > 60,