title: Classification of cancer types by measuring variants of host response proteins using SELDI serum assays.
abstract: Protein expression profiling has been increasingly used to discover and characterize biomarkers that can be used for diagnostic, prognostic or therapeutic purposes. Most proteomic studies published to date have identified relatively abundant host response proteins as candidate biomarkers, which are often dismissed because of an apparent lack of specificity. We demonstrate that 2 host response proteins previously identified as candidate markers for early stage ovarian cancer, transthyretin and inter-alpha trypsin inhibitor heavy chain 4 (ITIH4), are posttranslationally modified. These modifications include proteolytic truncation, cysteinylation and glutathionylation. Assays using Surface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS) may provide a means to confer specificity to these proteins because of their ability to detect and quantitate multiple posttranslationally modified forms of these proteins in a single assay. Quantitative measurements of these modifications using chromatographic and antibody-based ProteinChip array assays reveal that these posttranslational modifications occur to different extents in different cancers and that multivariate analysis permits the derivation of algorithms to improve the classification of these cancers. We have termed this process host response protein amplification cascade (HRPAC), since the process of synthesis, posttranslational modification and metabolism of host response proteins amplifies the signal of potentially low-abundant biologically active disease markers such as enzymes.
authors.affiliation: Ciphergen Biosystems, Fremont, CA 94555, USA. efung@ciphergen.com
authors.forename: Eric T
authors.initials: ET
authors.lastname: Fung
authors.forename: Tai-Tung
authors.initials: TT
authors.lastname: Yip
authors.forename: Lee
authors.initials: L
authors.lastname: Lomas
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Christine
authors.initials: C
authors.lastname: Yip
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Meng
authors.forename: Shanhua
authors.initials: S
authors.lastname: Lin
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Chan
authors.forename: Scot R
authors.initials: SR
authors.lastname: Weinberger
mesh_terms: D000465:Algorithms; D000510:Alpha-Globulins / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000276:immunology; D003110:Colonic Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D010051:Ovarian Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000276:immunology; D011228:Prealbumin / Q000032:analysis / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000276:immunology; D040081:Protein Array Analysis; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000510:Alpha-Globulins; D014408:Biomarkers, Tumor; D011228:Prealbumin; C011877:inter-alpha-inhibitor