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Advances in Proteomic Technologies and Its Contribution to the Field of Cancer.

Mesri M - Adv Med (2014)

Bottom Line: As such, proteomics can translate basic science discoveries into the clinical practice of precision medicine.The proteomic field has progressed at a fast rate over the past five years in technology, breadth and depth of applications in all areas of the bioscience.Some of the previously experimental technical approaches are considered the gold standard today, and the community is now trying to come to terms with the volume and complexity of the data generated.

View Article: PubMed Central - PubMed

Affiliation: Office of Cancer Clinical Proteomics Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

ABSTRACT
Systematic studies of the cancer genome have generated a wealth of knowledge in recent years. These studies have uncovered a number of new cancer genes not previously known to be causal targets in cancer. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies are not widely available for most cancers. Precision care plans still must be developed by understanding and implementing basic science research into clinical treatment. Proteomics is continuing to make major strides in the discovery of fundamental biological processes as well as more recent transition into an assay platform capable of measuring hundreds of proteins in any biological system. As such, proteomics can translate basic science discoveries into the clinical practice of precision medicine. The proteomic field has progressed at a fast rate over the past five years in technology, breadth and depth of applications in all areas of the bioscience. Some of the previously experimental technical approaches are considered the gold standard today, and the community is now trying to come to terms with the volume and complexity of the data generated. Here I describe contribution of proteomics in general and biological mass spectrometry in particular to cancer research, as well as related major technical and conceptual developments in the field.

No MeSH data available.


Related in: MedlinePlus

Increase in number of MRM publications in PubMed over the past decade.
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fig5: Increase in number of MRM publications in PubMed over the past decade.

Mentions: MRM-MS method for quantification of biomolecules has been long in use (e.g., drug metabolites [124, 125], hormones [126], protein degradation products [127], and pesticides [128]) with great precision (CV < 5%) but has only recently been adopted for protein and peptide measurements. Stable isotope dilution (SID) multiple reaction monitoring MS (SID-MRM-MS) has emerged as one of the powerful targeted proteomic tools in the past few years. MRM mass spectrometry is being rapidly adopted by the biomedical research community as shown by increase in the number of publications in this area over the past decade (Figure 5). It has the advantage of accurately calculating protein concentrations in a multiplexed and high throughput manner, while avoiding many of the issues associated with antibody-based protein quantification [117]. SID-MRM-MS protein assays are based upon the quantitation of signature tryptic peptides as surrogates that uniquely represent the protein candidates of interest [129, 130]. To improve the specificity of the quantitative measurement for targeted analytes in MRM-based assays, a selection of three to five peptides per protein is selected [131]. Moreover, known quantities of synthetic stable isotope-labeled peptides (heavy peptides), corresponding to each endogenous peptide, are used as internal standard peptides (i.e., stable isotope-labeled internal standards or SIS). These SISs are identical to their endogenous analyte peptide counterparts with the exception of their masses (usually 6–10 Da more). For quantitation, specific fragment ion signals derived from the endogenous unlabeled peptides are compared to those from the spike-in SISs as ratios and are used to calculate the concentration of that protein [130, 131]. In SID-MRM-MS, the presence of SIS can calculate more accurate ratios with high sensitivity and across a wide dynamic range. The absence of an endogenous peptide signal typically means that the concentration of the peptide in the sample is below the detection limit of the instrument. Additionally the amount of SIS added should be optimized empirically in a preliminary study as this depends on the protein's individual relative abundance within a sample. High sensitivity and precision, combined with specific quantitation in a multiplex fashion, make MRM assays attractive for translational and clinical research [132, 133]. Targeted proteomics has also been recognized by the journal Nature Methods as the method of the year in 2012 [134].


Advances in Proteomic Technologies and Its Contribution to the Field of Cancer.

Mesri M - Adv Med (2014)

Increase in number of MRM publications in PubMed over the past decade.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590950&req=5

fig5: Increase in number of MRM publications in PubMed over the past decade.
Mentions: MRM-MS method for quantification of biomolecules has been long in use (e.g., drug metabolites [124, 125], hormones [126], protein degradation products [127], and pesticides [128]) with great precision (CV < 5%) but has only recently been adopted for protein and peptide measurements. Stable isotope dilution (SID) multiple reaction monitoring MS (SID-MRM-MS) has emerged as one of the powerful targeted proteomic tools in the past few years. MRM mass spectrometry is being rapidly adopted by the biomedical research community as shown by increase in the number of publications in this area over the past decade (Figure 5). It has the advantage of accurately calculating protein concentrations in a multiplexed and high throughput manner, while avoiding many of the issues associated with antibody-based protein quantification [117]. SID-MRM-MS protein assays are based upon the quantitation of signature tryptic peptides as surrogates that uniquely represent the protein candidates of interest [129, 130]. To improve the specificity of the quantitative measurement for targeted analytes in MRM-based assays, a selection of three to five peptides per protein is selected [131]. Moreover, known quantities of synthetic stable isotope-labeled peptides (heavy peptides), corresponding to each endogenous peptide, are used as internal standard peptides (i.e., stable isotope-labeled internal standards or SIS). These SISs are identical to their endogenous analyte peptide counterparts with the exception of their masses (usually 6–10 Da more). For quantitation, specific fragment ion signals derived from the endogenous unlabeled peptides are compared to those from the spike-in SISs as ratios and are used to calculate the concentration of that protein [130, 131]. In SID-MRM-MS, the presence of SIS can calculate more accurate ratios with high sensitivity and across a wide dynamic range. The absence of an endogenous peptide signal typically means that the concentration of the peptide in the sample is below the detection limit of the instrument. Additionally the amount of SIS added should be optimized empirically in a preliminary study as this depends on the protein's individual relative abundance within a sample. High sensitivity and precision, combined with specific quantitation in a multiplex fashion, make MRM assays attractive for translational and clinical research [132, 133]. Targeted proteomics has also been recognized by the journal Nature Methods as the method of the year in 2012 [134].

Bottom Line: As such, proteomics can translate basic science discoveries into the clinical practice of precision medicine.The proteomic field has progressed at a fast rate over the past five years in technology, breadth and depth of applications in all areas of the bioscience.Some of the previously experimental technical approaches are considered the gold standard today, and the community is now trying to come to terms with the volume and complexity of the data generated.

View Article: PubMed Central - PubMed

Affiliation: Office of Cancer Clinical Proteomics Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

ABSTRACT
Systematic studies of the cancer genome have generated a wealth of knowledge in recent years. These studies have uncovered a number of new cancer genes not previously known to be causal targets in cancer. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies are not widely available for most cancers. Precision care plans still must be developed by understanding and implementing basic science research into clinical treatment. Proteomics is continuing to make major strides in the discovery of fundamental biological processes as well as more recent transition into an assay platform capable of measuring hundreds of proteins in any biological system. As such, proteomics can translate basic science discoveries into the clinical practice of precision medicine. The proteomic field has progressed at a fast rate over the past five years in technology, breadth and depth of applications in all areas of the bioscience. Some of the previously experimental technical approaches are considered the gold standard today, and the community is now trying to come to terms with the volume and complexity of the data generated. Here I describe contribution of proteomics in general and biological mass spectrometry in particular to cancer research, as well as related major technical and conceptual developments in the field.

No MeSH data available.


Related in: MedlinePlus