BACKGROUND: Many high-abundant acute phase reactants have been previously detected as potential breast cancer biomar-kers. However, they are unlikely to be specific for breast cancer. Cancer-specific biomarkers are thought to be among the lower abundant proteins. METHODS: We aimed to detect lower abundant discriminating proteins by performing serum fractionation by strong anion exchange chromatography preceding protein profiling with SELDI-TOF MS. In a pilot study, we tested the different fractions resulting from fractionation, on several array types. Fraction 3 on IMAC30 and Fraction 6 on Q10 yielded the most discriminative proteins and were used for serum protein profiling of 73 incident breast cancer cases and 73 matched controls. RESULTS: Eight peaks showed statistically significantly different intensities between cases and controls (P⧁0.05), and had less than 10% chance to be a false-positive finding. Seven of these were tentatively identified as apolipoprotein C-II (m/z 8,909), oxidized apolipoprotein C-II (m/z 8,925), apolipoprotein C-III (m/z 8,746), fragment of coagulation factor XIIIa (m/z 3,959), heterodimer of apolipoprotein A-I and apolipoprotein A-II (m/z 45,435), hemoglobin B-chain (m/z 15,915), and post-translational modified hemoglobin (m/z 15,346). CONCLUSION: By extensive serum fractionation, we detected many more proteins than in previous studies without fractionation. However, discriminating proteins were still high abundant. Results indicate that either lower abundant proteins are less distinctive, or more rigorous fractionation and selective protein depletion, or a more sensitive assay, are needed to detect lower abundant discriminative proteins.
BACKGROUND: Many high-abundant acute phase reactants have been previously detected as potential breast cancer biomar-kers. However, they are unlikely to be specific for breast cancer. Cancer-specific biomarkers are thought to be among the lower abundant proteins. METHODS: We aimed to detect lower abundant discriminating proteins by performing serum fractionation by strong anion exchange chromatography preceding protein profiling with SELDI-TOF MS. In a pilot study, we tested the different fractions resulting from fractionation, on several array types. Fraction 3 on IMAC30 and Fraction 6 on Q10 yielded the most discriminative proteins and were used for serum protein profiling of 73 incident breast cancer cases and 73 matched controls. RESULTS: Eight peaks showed statistically significantly different intensities between cases and controls (P⧁0.05), and had less than 10% chance to be a false-positive finding. Seven of these were tentatively identified as apolipoprotein C-II (m/z 8,909), oxidized apolipoprotein C-II (m/z 8,925), apolipoprotein C-III (m/z 8,746), fragment of coagulation factor XIIIa (m/z 3,959), heterodimer of apolipoprotein A-I and apolipoprotein A-II (m/z 45,435), hemoglobin B-chain (m/z 15,915), and post-translational modified hemoglobin (m/z 15,346). CONCLUSION: By extensive serum fractionation, we detected many more proteins than in previous studies without fractionation. However, discriminating proteins were still high abundant. Results indicate that either lower abundant proteins are less distinctive, or more rigorous fractionation and selective protein depletion, or a more sensitive assay, are needed to detect lower abundant discriminative proteins.
Authors: Josep Villanueva; David R Shaffer; John Philip; Carlos A Chaparro; Hediye Erdjument-Bromage; Adam B Olshen; Martin Fleisher; Hans Lilja; Edi Brogi; Jeff Boyd; Marta Sanchez-Carbayo; Eric C Holland; Carlos Cordon-Cardo; Howard I Scher; Paul Tempst Journal: J Clin Invest Date: 2006-01 Impact factor: 14.808
Authors: Marie-Christine W Gast; Carla H van Gils; Lodewijk F A Wessels; Nathan Harris; Johannes M G Bonfrer; Emiel J Th Rutgers; Jan H M Schellens; Jos H Beijnen Journal: Clin Chem Lab Med Date: 2009 Impact factor: 3.694
Authors: Jin Song; Manisha Patel; C Nicole Rosenzweig; Yee Chan-Li; Lori J Sokoll; Eric T Fung; Nam-Ho Choi-Miura; Michael Goggins; Daniel W Chan; Zhen Zhang Journal: Clin Chem Date: 2006-03-30 Impact factor: 8.327