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The current state of proteomics in GI oncology.

Lin Y, Dynan WS, Lee JR, Zhu ZH, Schade RR - Dig. Dis. Sci. (2008)

Bottom Line: Proteomics refers to the study of the entire set of proteins in a given cell or tissue.In this article, we introduce the commonly adopted proteomic technologies and describe results of a comprehensive review of studies that have applied these technologies to GI oncology, with a particular emphasis on developments in the last 3 years.We discuss reasons why the more than 130 studies to date have had little discernible clinical impact, and we outline steps that may allow proteomics to realize its promise for early detection of disease, monitoring of disease recurrence, and identification of targets for individualized therapy.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.

ABSTRACT
Proteomics refers to the study of the entire set of proteins in a given cell or tissue. With the extensive development of protein separation, mass spectrometry, and bioinformatics technologies, clinical proteomics has shown its potential as a powerful approach for biomarker discovery, particularly in the area of oncology. More than 130 exploratory studies have defined candidate markers in serum, gastrointestinal (GI) fluids, or cancer tissue. In this article, we introduce the commonly adopted proteomic technologies and describe results of a comprehensive review of studies that have applied these technologies to GI oncology, with a particular emphasis on developments in the last 3 years. We discuss reasons why the more than 130 studies to date have had little discernible clinical impact, and we outline steps that may allow proteomics to realize its promise for early detection of disease, monitoring of disease recurrence, and identification of targets for individualized therapy.

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Schematic illustration of ICAT procedure. a ICAT reagent combines three moieties: a biotin tag, a heavy or light isotope-tagged linker, and a thiol-specific reactive group. b Samples, labeled with heavy- or light-isotope ICAT reagent are mixed and digested. Tagged peptides are isolated by avidin affinity chromatography and analyzed by LC-MS. The relative abundance of heavy and light isotope peaks for each peptide is then measured. Peptides of interest can be identified by MS/MS analysis
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Fig5: Schematic illustration of ICAT procedure. a ICAT reagent combines three moieties: a biotin tag, a heavy or light isotope-tagged linker, and a thiol-specific reactive group. b Samples, labeled with heavy- or light-isotope ICAT reagent are mixed and digested. Tagged peptides are isolated by avidin affinity chromatography and analyzed by LC-MS. The relative abundance of heavy and light isotope peaks for each peptide is then measured. Peptides of interest can be identified by MS/MS analysis

Mentions: Isotope-coded affinity tag (ICAT) technology is the analogous method for the bottom-up approach. The ICAT reagent combines three moieties: a biotin group, a heavy or light isotope-tagged linker (e.g., containing 2H vs. 1H, or 13C vs. 12C), and a thiol-specific reactive group that reacts with cysteine in the protein sample (Fig. 5a) [29]. Two samples, pre-labeled with heavy- or light-isotope ICAT reagent, are mixed and proteolytically digested (Fig. 5b). Tagged peptides are isolated by avidin affinity chromatography and analyzed by LC-MS [30]. The relative abundance of heavy and light isotope peaks for each peptide provides an accurate measure of the relative abundance of the peptide in different samples. A variation, isotope-coded protein label (ICPL) [31], is based on isotopic labeling of free amino groups in proteins, which are more abundant than thiols. Another variation, isobaric tags for relative and absolute quantification (iTRAQ) allows multiplexing of up to four samples simultaneously [32].Fig. 5


The current state of proteomics in GI oncology.

Lin Y, Dynan WS, Lee JR, Zhu ZH, Schade RR - Dig. Dis. Sci. (2008)

Schematic illustration of ICAT procedure. a ICAT reagent combines three moieties: a biotin tag, a heavy or light isotope-tagged linker, and a thiol-specific reactive group. b Samples, labeled with heavy- or light-isotope ICAT reagent are mixed and digested. Tagged peptides are isolated by avidin affinity chromatography and analyzed by LC-MS. The relative abundance of heavy and light isotope peaks for each peptide is then measured. Peptides of interest can be identified by MS/MS analysis
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045515&req=5

Fig5: Schematic illustration of ICAT procedure. a ICAT reagent combines three moieties: a biotin tag, a heavy or light isotope-tagged linker, and a thiol-specific reactive group. b Samples, labeled with heavy- or light-isotope ICAT reagent are mixed and digested. Tagged peptides are isolated by avidin affinity chromatography and analyzed by LC-MS. The relative abundance of heavy and light isotope peaks for each peptide is then measured. Peptides of interest can be identified by MS/MS analysis
Mentions: Isotope-coded affinity tag (ICAT) technology is the analogous method for the bottom-up approach. The ICAT reagent combines three moieties: a biotin group, a heavy or light isotope-tagged linker (e.g., containing 2H vs. 1H, or 13C vs. 12C), and a thiol-specific reactive group that reacts with cysteine in the protein sample (Fig. 5a) [29]. Two samples, pre-labeled with heavy- or light-isotope ICAT reagent, are mixed and proteolytically digested (Fig. 5b). Tagged peptides are isolated by avidin affinity chromatography and analyzed by LC-MS [30]. The relative abundance of heavy and light isotope peaks for each peptide provides an accurate measure of the relative abundance of the peptide in different samples. A variation, isotope-coded protein label (ICPL) [31], is based on isotopic labeling of free amino groups in proteins, which are more abundant than thiols. Another variation, isobaric tags for relative and absolute quantification (iTRAQ) allows multiplexing of up to four samples simultaneously [32].Fig. 5

Bottom Line: Proteomics refers to the study of the entire set of proteins in a given cell or tissue.In this article, we introduce the commonly adopted proteomic technologies and describe results of a comprehensive review of studies that have applied these technologies to GI oncology, with a particular emphasis on developments in the last 3 years.We discuss reasons why the more than 130 studies to date have had little discernible clinical impact, and we outline steps that may allow proteomics to realize its promise for early detection of disease, monitoring of disease recurrence, and identification of targets for individualized therapy.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.

ABSTRACT
Proteomics refers to the study of the entire set of proteins in a given cell or tissue. With the extensive development of protein separation, mass spectrometry, and bioinformatics technologies, clinical proteomics has shown its potential as a powerful approach for biomarker discovery, particularly in the area of oncology. More than 130 exploratory studies have defined candidate markers in serum, gastrointestinal (GI) fluids, or cancer tissue. In this article, we introduce the commonly adopted proteomic technologies and describe results of a comprehensive review of studies that have applied these technologies to GI oncology, with a particular emphasis on developments in the last 3 years. We discuss reasons why the more than 130 studies to date have had little discernible clinical impact, and we outline steps that may allow proteomics to realize its promise for early detection of disease, monitoring of disease recurrence, and identification of targets for individualized therapy.

Show MeSH
Related in: MedlinePlus