MALDI imaging mass spectrometry in ovarian cancer for tracking, identifying, and validating biomarkers

• Published in: Medical science monitor Vol. 16; no. 8; pp. BR233 - BR245
• Main Authors: El Ayed, Mohamed, Bonnel, David, Longuespée, Remi, Castelier, Céline, Franck, Julien, Vergara, Daniele, Desmons, Annie, Tasiemski, Aurélie, Kenani, Abderraouf, Vinatier, Denis, Day, Robert, Fournier, Isabelle, Salzet, Michel
• Format: Journal Article Web Resource
• Language: English
• Published: United States Medical Science International Publishing 01.08.2010
• Subjects: Adenocarcinoma, Mucinous; Amino Acid Sequence; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Biomarkers, Tumor; Biomarkers, Tumor - chemistry; Biomarkers, Tumor - metabolism; Female; Gene Expression Regulation, Neoplastic; Humans; Life Sciences; Molecular Sequence Data; Molecular Weight; Nanotechnology; Neoplasm Proteins; Neoplasm Proteins - chemistry; Neoplasm Proteins - metabolism; Neoplasm Staging; Ovarian Neoplasms; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Principal Component Analysis; Reproducibility of Results; Sciences du vivant; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods
• ISSN: 1234-1010; 1643-3750; 1643-3750

Among biomarkers, cancer-antigen 125 (CA-125) is the most studied. We propose an analytical tool to track ovarian carcinoma biomarkers, that is, the MALDI mass spectrometry imaging. Ovarian carcinomas and benign ovaries were directly analyzed by MALDI-TOF-MS. After automatic profiling and mass spectrometry imaging analyses, hierarchical clustering based on principal component analysis in nonsupervised mode was carried out. On the same samples, preparations were performed to investigate peptides, then proteins, followed by high mass proteins, in an automatic profiling to specific signatures for diagnosis. Using tissue bottom-up strategy on tissue digestion, and mass spectrometry imaging after by shotgun sequencing by nalano-LC-IT-MS in MS/MS mode from washing samples from on tissue digested peptides, several biomarkers were found. A list of specific biomarkers from the ovarian carcinoma regions was obtained and classified as proteins associated with cell proliferation, involved in immune response modulation, signaling to the cytoskeleton, and tumor progression. These specific biomarkers were then validated by immunocytochemistry using Tag-mass technology, cell biology, Western blot, and by PCR (using SKOV-3 ovarian epithelial cancer cells). A link between the immune regulation (innate immunity, tolerance) and virus cause is also discussed. From the biomarkers identified, proteins involved in immune response modulation and cell proliferation have been pointed out in this study. Two new markers have been identified using such a strategy, that is, fragment C-terminal of the PSME1 (Reg-Alpha) and mucin-9.