The Experts below are selected from a list of 156 Experts worldwide ranked by ideXlab platform

Brian B. Haab - One of the best experts on this subject based on the ideXlab platform.

  • Diverse monoclonal antibodies against the CA 19-9 Antigen show variation in binding specificity with consequences for cliniCAl interpretation.
    Proteomics, 2012
    Co-Authors: Katie Partyka, Kevin A. Maupin, Randall E. Brand, Brian B. Haab
    Abstract:

    The CA 19-9 Antigen is currently the best individual marker for the detection of pancreatic CAncer. In order to optimize the CA 19-9 assay and to develop approaches to further improve CAncer detection, it is important to understand the specificity differences between CA 19-9 antibodies and the consequential affect on biomarker performance. Antibody arrays enabled multiplexed comparisons between five different CA 19-9 antibodies used in the analysis of plasma samples from pancreatic CAncer patients and controls. Major differences were observed between antibodies in their detection of particular patient samples. GlyCAn array analysis revealed that certain antibodies were highly specific for the CAnoniCAl CA 19-9 epitope, sialyl-Lewis A, while others bound sialyl-Lewis A in addition to a related structure CAlled sialyl-Lewis C and modifiCAtion with Nue5Gc. In a much larger patient cohort, we confirmed the binding of sialyl-Lewis C glyCAn by one of the antibodies and showed that the broader specificity led to the detection of an increased number of CAncer patients without increasing detection of pancreatitis patient samples. This work demonstrates that variation between antibody specificity for CAncer-associated glyCAns CAn have signifiCAnt impliCAtions for biomarker performance and highlights the value of characterizing and detecting the range of glyCAn structures that are elevated in CAncer.

  • IdentifiCAtion of blood-protein CArriers of the CA 19-9 Antigen and characterization of prevalence in pancreatic diseases
    Proteomics, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Mary C. Hurley, Philip C. Andrews, Karen L. Kaul, A. James Moser, Herbert J. Zeh, Randall E. Brand, Brian B. Haab
    Abstract:

    The current best serum marker for pancreatic CAncer, CA 19-9, detects a CArbohydrate Antigen on multiple protein CArriers. Better knowledge of the protein CArriers of the CA 19-9 Antigen in various disease states may lead to improved diagnostic tests. To identify proteins that CArry the CA 19-9 Antigen, we immunoprecipitated the CA 19-9 Antigen from pooled sera and identified the associated proteins using MS. Among the high-confidence identifiCAtions, we confirmed the presence of the CA 19-9 Antigen on Apolipoprotein B-100 by antibody arrays and Western blot and on kininogen, ARVCF, and Apolipoprotein E by antibody arrays. We characterized the frequency and levels of the CA 19-9 Antigen on the four proteins across various patient groups (pancreatic CAncer, pancreatitis, and healthy controls) using antibody arrays. Nearly, 10-25% of the subjects showed elevations of the Antigen on each protein, but the elevations were not associated with disease state or total CA 19-9 levels. These results contribute to our knowledge of the CArrier proteins of an important functional glyCAn and the rate at which the glyCAn is displayed. This work also demonstrates a strategy for using the complementary methods of MS and antibody microarrays to identify protein CArriers of glyCAns and assess the diagnostic value of measuring glyCAns on individual proteins.

  • Abstract 2216: Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 Antigen on specific protein CArriers
    Clinical Research, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Randall E. Brand, Michelle A. Anderson, Dean E. Brenner, Diane M. Simeone, Ziding Feng, Brian B. Haab
    Abstract:

    Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL The CA 19-9 assay detects a CArbohydrate Antigen on multiple protein CArriers, some of which may be preferential CArriers of the Antigen in CAncer. We tested the hypothesis that the measurement of the CA 19-9 Antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 Antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenoCArcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 420 individual samples. The measurement of the CA 19-9 Antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (79-88% sensitivity at 75% specificity), owing to diversity among patients in their CA 19-9 protein CArriers. However, a subset of CAncer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 Antigen specifiCAlly on the proteins MUC1, MUC5AC, or MUC16 in all three sample sets. By combining measurements of total CA 19-9 with CA 19-9 on these individual proteins, the sensitivity of CAncer detection was raised to 85-100% in the three sample sets, at a specificity of 75%. This finding demonstrates the potential value of measuring glyCAns on specific proteins for improving biomarker performance. Furthermore, the definition of subgroups of patients based on the protein CArriers of the CA 19-9 Antigen and other glyCAns will guide the further development of informative biomarker panels. Diagnostic tests with improved sensitivity for detecting pancreatic CAncer could have important appliCAtions for improving the treatment and management of patients suffering from this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the AmeriCAn Association for CAncer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; CAncer Res 2011;71(8 Suppl):Abstract nr 2216. doi:10.1158/1538-7445.AM2011-2216

  • Abstract 5567: Pancreatic disease-specific CArriers of the CA 19-9 Antigen identified by antibody microarrays and mass spectrometry
    Cancer Chemistry, 2010
    Co-Authors: Tingting Yue, Mary C. Hurley, Philip C. Andrews, Randel E. Brand, Brian B. Haab
    Abstract:

    Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Distinguishing patients with malignant pancreatic tumors from those with benign conditions is critiCAl for doctors to make proper treatment decisions. However, this process is usually costly and invasive due to the lack of a simple detection method such as a blood test. The current standard serologiCAl biomarker of pancreatic CAncer, the CA 19-9 Antigen, is not accurate enough for early diagnosis due to its ocCAsional elevation in benign pancreatic diseases. The CA 19-9 Antigen is a CArbohydrate epitope found on multiple protein CArriers. We sought to determine whether the protein CArriers of the CA 19-9 Antigen are different between benign and malignant pancreatic disease, and whether these differences could be harnessed to develop improved biomarkers. Two approaches were used to investigate this question. In the first, we used antibody microarrays to CApture multiple different mucins from the sera of early-stage pancreatic CAncer patients (n = 33), late-stage pancreatic CAncer patients (n = 17), pancreatitis patients (n = 38), and healthy control subjects (n = 20), and we probed the level of the CA 19-9 Antigen on the CAptured proteins using a monoclonal antibody. Pancreatic CAncer progression was associated with a shift in CA 19-9 CArriers from MUC16 to MUC1 and MUC5AC. Certain monoclonal antibodies CAptured glycoforms of MUC1 that predominantly CArried CA 19-9 in the CAncer patients. BeCAuse of that relationship, the detection of CA 19-9 on specific protein glycoforms improved the discrimination of CAncer from control subjects over total CA 19-9 (AUC= 0.93 vs. AUC=0.86. In the second approach, we immunoprecipitated CA19-9 CArrier proteins from pooled sera of late-stage CAncer, early-stage CAncer, pancreatitis, and control subjects, followed by deglycosylation and mass spectrometry (MALDI/TOF/TOF). Several proteins were identified in the sera of the CAncer patients but not in the sera of pancreatitis or control subjects, indiCAting the possible identifiCAtion of state-specific CArriers of CA 19-9. Ongoing studies are aimed at verifying these identifiCAtions and testing performance as biomarkers of pancreatic CAncer. These findings may lead to more accurate methods of discriminating benign from malignant pancreatic disease, which would improve the ability to render proper CAre to patients at the earliest possible stages. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the AmeriCAn Association for CAncer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; CAncer Res 2010;70(8 Suppl):Abstract nr 5567.

Katie Partyka - One of the best experts on this subject based on the ideXlab platform.

  • Diverse monoclonal antibodies against the CA 19-9 Antigen show variation in binding specificity with consequences for cliniCAl interpretation.
    Proteomics, 2012
    Co-Authors: Katie Partyka, Kevin A. Maupin, Randall E. Brand, Brian B. Haab
    Abstract:

    The CA 19-9 Antigen is currently the best individual marker for the detection of pancreatic CAncer. In order to optimize the CA 19-9 assay and to develop approaches to further improve CAncer detection, it is important to understand the specificity differences between CA 19-9 antibodies and the consequential affect on biomarker performance. Antibody arrays enabled multiplexed comparisons between five different CA 19-9 antibodies used in the analysis of plasma samples from pancreatic CAncer patients and controls. Major differences were observed between antibodies in their detection of particular patient samples. GlyCAn array analysis revealed that certain antibodies were highly specific for the CAnoniCAl CA 19-9 epitope, sialyl-Lewis A, while others bound sialyl-Lewis A in addition to a related structure CAlled sialyl-Lewis C and modifiCAtion with Nue5Gc. In a much larger patient cohort, we confirmed the binding of sialyl-Lewis C glyCAn by one of the antibodies and showed that the broader specificity led to the detection of an increased number of CAncer patients without increasing detection of pancreatitis patient samples. This work demonstrates that variation between antibody specificity for CAncer-associated glyCAns CAn have signifiCAnt impliCAtions for biomarker performance and highlights the value of characterizing and detecting the range of glyCAn structures that are elevated in CAncer.

  • Abstract B6: Genotype-selected biomarkers for the accurate diagnosis of pancreatic CAncer.
    Diagnosis, 2012
    Co-Authors: Huiyuan Tang, Katie Partyka, Kevin A. Maupin, Randall E. Brand, Brain Haab
    Abstract:

    The CA 19-9 assay is the current best serum/plasma marker for pancreatic CAncer and CAn be an accurate indiCAtor of CAncer for many patients. However, it is not effective for patients who harbor germline DNA mutations that result in absent or weakened expression of CA 19-9. These mutations are present in the enzymes that synthesize the CA 19-9 Antigen, which is a glyCAn structure CAlled sialyl-Lewis A. Here we tested the hypothesis that the stratifiCAtion of patients by specific genotypes and the use of optimized biomarkers for each genotype CAn yield improved diagnostic performance. We acquired the genotypes of 162 pancreatic CAncer and control subjects for five different genes involved in the biosynthesis of the CA 19-9 Antigen. The CA 19-9 levels in the blood plasma of these patients were accurately predicted by specific SNPs in the genes fucosyltransferase 2 and fucosyltransferase 3 (FUT2 and FUT3). The patients were subdivided into four groups based on these genotypes, and marker discovery and optimization was performed separately for each group using measurements from dozens of glyCAn-based markers. The FUT2 homozygous mutant (FUT2-/-) subjects were perfectly diagnosed (100% accurate discrimination of CAncer from controls) using CA 19-9 alone, whereas FUT2+/- and FUT2 WT subjects were accurately diagnosed using CA 19-9 in combination with two other markers selected for each group. The FUT3-/- patients were accurately diagnosed using a new biomarker, a particular glycosylation variant of the MUC1 protein. The overall performance of the genotype-selected biomarker panel was 100% sensitivity (93/93 CAncer CAses correctly detected) and 96% specificity (66/69 controls correct). This performance signifiCAntly outperforms CA 19-9 alone (87% sensitivity and 84% specificity) and biomarker panels that do not incorporate genotype selection. Validation experiments using 40 additional unblinded samples and 200 additional blinded samples are underway. Genotype-selected biomarkers show the potential for signifiCAntly improving upon conventional biomarker strategies. Citation Format: Huiyuan Tang, Katie Partyka, Kevin Maupin, Randall Brand, Brain Haab. Genotype-selected biomarkers for the accurate diagnosis of pancreatic CAncer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic CAncer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; CAncer Res 2012;72(12 Suppl):Abstract nr B6.

  • Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 Antigen on specific protein CArriers.
    PloS one, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Karen L. Kaul, Herbert J. Zeh, Brian A Fallon, Michelle A. Anderson, Dean E. Brenner, A. James Moser
    Abstract:

    The CA 19-9 assay detects a CArbohydrate Antigen on multiple protein CArriers, some of which may be preferential CArriers of the Antigen in CAncer. We tested the hypothesis that the measurement of the CA 19-9 Antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 Antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenoCArcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 Antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage CAncer), owing to diversity among patients in their CA 19-9 protein CArriers. However, a subset of CAncer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 Antigen specifiCAlly on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of CAncer detection was improved relative to CA 19-9 alone in each sample set, achieving 67–80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glyCAns on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic CAncer could have important appliCAtions for improving the treatment and management of patients suffering from this disease.

  • IdentifiCAtion of blood-protein CArriers of the CA 19-9 Antigen and characterization of prevalence in pancreatic diseases
    Proteomics, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Mary C. Hurley, Philip C. Andrews, Karen L. Kaul, A. James Moser, Herbert J. Zeh, Randall E. Brand, Brian B. Haab
    Abstract:

    The current best serum marker for pancreatic CAncer, CA 19-9, detects a CArbohydrate Antigen on multiple protein CArriers. Better knowledge of the protein CArriers of the CA 19-9 Antigen in various disease states may lead to improved diagnostic tests. To identify proteins that CArry the CA 19-9 Antigen, we immunoprecipitated the CA 19-9 Antigen from pooled sera and identified the associated proteins using MS. Among the high-confidence identifiCAtions, we confirmed the presence of the CA 19-9 Antigen on Apolipoprotein B-100 by antibody arrays and Western blot and on kininogen, ARVCF, and Apolipoprotein E by antibody arrays. We characterized the frequency and levels of the CA 19-9 Antigen on the four proteins across various patient groups (pancreatic CAncer, pancreatitis, and healthy controls) using antibody arrays. Nearly, 10-25% of the subjects showed elevations of the Antigen on each protein, but the elevations were not associated with disease state or total CA 19-9 levels. These results contribute to our knowledge of the CArrier proteins of an important functional glyCAn and the rate at which the glyCAn is displayed. This work also demonstrates a strategy for using the complementary methods of MS and antibody microarrays to identify protein CArriers of glyCAns and assess the diagnostic value of measuring glyCAns on individual proteins.

  • Abstract 2216: Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 Antigen on specific protein CArriers
    Clinical Research, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Randall E. Brand, Michelle A. Anderson, Dean E. Brenner, Diane M. Simeone, Ziding Feng, Brian B. Haab
    Abstract:

    Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL The CA 19-9 assay detects a CArbohydrate Antigen on multiple protein CArriers, some of which may be preferential CArriers of the Antigen in CAncer. We tested the hypothesis that the measurement of the CA 19-9 Antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 Antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenoCArcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 420 individual samples. The measurement of the CA 19-9 Antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (79-88% sensitivity at 75% specificity), owing to diversity among patients in their CA 19-9 protein CArriers. However, a subset of CAncer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 Antigen specifiCAlly on the proteins MUC1, MUC5AC, or MUC16 in all three sample sets. By combining measurements of total CA 19-9 with CA 19-9 on these individual proteins, the sensitivity of CAncer detection was raised to 85-100% in the three sample sets, at a specificity of 75%. This finding demonstrates the potential value of measuring glyCAns on specific proteins for improving biomarker performance. Furthermore, the definition of subgroups of patients based on the protein CArriers of the CA 19-9 Antigen and other glyCAns will guide the further development of informative biomarker panels. Diagnostic tests with improved sensitivity for detecting pancreatic CAncer could have important appliCAtions for improving the treatment and management of patients suffering from this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the AmeriCAn Association for CAncer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; CAncer Res 2011;71(8 Suppl):Abstract nr 2216. doi:10.1158/1538-7445.AM2011-2216

Kevin A. Maupin - One of the best experts on this subject based on the ideXlab platform.

  • Diverse monoclonal antibodies against the CA 19-9 Antigen show variation in binding specificity with consequences for cliniCAl interpretation.
    Proteomics, 2012
    Co-Authors: Katie Partyka, Kevin A. Maupin, Randall E. Brand, Brian B. Haab
    Abstract:

    The CA 19-9 Antigen is currently the best individual marker for the detection of pancreatic CAncer. In order to optimize the CA 19-9 assay and to develop approaches to further improve CAncer detection, it is important to understand the specificity differences between CA 19-9 antibodies and the consequential affect on biomarker performance. Antibody arrays enabled multiplexed comparisons between five different CA 19-9 antibodies used in the analysis of plasma samples from pancreatic CAncer patients and controls. Major differences were observed between antibodies in their detection of particular patient samples. GlyCAn array analysis revealed that certain antibodies were highly specific for the CAnoniCAl CA 19-9 epitope, sialyl-Lewis A, while others bound sialyl-Lewis A in addition to a related structure CAlled sialyl-Lewis C and modifiCAtion with Nue5Gc. In a much larger patient cohort, we confirmed the binding of sialyl-Lewis C glyCAn by one of the antibodies and showed that the broader specificity led to the detection of an increased number of CAncer patients without increasing detection of pancreatitis patient samples. This work demonstrates that variation between antibody specificity for CAncer-associated glyCAns CAn have signifiCAnt impliCAtions for biomarker performance and highlights the value of characterizing and detecting the range of glyCAn structures that are elevated in CAncer.

  • Abstract B6: Genotype-selected biomarkers for the accurate diagnosis of pancreatic CAncer.
    Diagnosis, 2012
    Co-Authors: Huiyuan Tang, Katie Partyka, Kevin A. Maupin, Randall E. Brand, Brain Haab
    Abstract:

    The CA 19-9 assay is the current best serum/plasma marker for pancreatic CAncer and CAn be an accurate indiCAtor of CAncer for many patients. However, it is not effective for patients who harbor germline DNA mutations that result in absent or weakened expression of CA 19-9. These mutations are present in the enzymes that synthesize the CA 19-9 Antigen, which is a glyCAn structure CAlled sialyl-Lewis A. Here we tested the hypothesis that the stratifiCAtion of patients by specific genotypes and the use of optimized biomarkers for each genotype CAn yield improved diagnostic performance. We acquired the genotypes of 162 pancreatic CAncer and control subjects for five different genes involved in the biosynthesis of the CA 19-9 Antigen. The CA 19-9 levels in the blood plasma of these patients were accurately predicted by specific SNPs in the genes fucosyltransferase 2 and fucosyltransferase 3 (FUT2 and FUT3). The patients were subdivided into four groups based on these genotypes, and marker discovery and optimization was performed separately for each group using measurements from dozens of glyCAn-based markers. The FUT2 homozygous mutant (FUT2-/-) subjects were perfectly diagnosed (100% accurate discrimination of CAncer from controls) using CA 19-9 alone, whereas FUT2+/- and FUT2 WT subjects were accurately diagnosed using CA 19-9 in combination with two other markers selected for each group. The FUT3-/- patients were accurately diagnosed using a new biomarker, a particular glycosylation variant of the MUC1 protein. The overall performance of the genotype-selected biomarker panel was 100% sensitivity (93/93 CAncer CAses correctly detected) and 96% specificity (66/69 controls correct). This performance signifiCAntly outperforms CA 19-9 alone (87% sensitivity and 84% specificity) and biomarker panels that do not incorporate genotype selection. Validation experiments using 40 additional unblinded samples and 200 additional blinded samples are underway. Genotype-selected biomarkers show the potential for signifiCAntly improving upon conventional biomarker strategies. Citation Format: Huiyuan Tang, Katie Partyka, Kevin Maupin, Randall Brand, Brain Haab. Genotype-selected biomarkers for the accurate diagnosis of pancreatic CAncer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic CAncer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; CAncer Res 2012;72(12 Suppl):Abstract nr B6.

  • Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 Antigen on specific protein CArriers.
    PloS one, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Karen L. Kaul, Herbert J. Zeh, Brian A Fallon, Michelle A. Anderson, Dean E. Brenner, A. James Moser
    Abstract:

    The CA 19-9 assay detects a CArbohydrate Antigen on multiple protein CArriers, some of which may be preferential CArriers of the Antigen in CAncer. We tested the hypothesis that the measurement of the CA 19-9 Antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 Antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenoCArcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 Antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage CAncer), owing to diversity among patients in their CA 19-9 protein CArriers. However, a subset of CAncer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 Antigen specifiCAlly on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of CAncer detection was improved relative to CA 19-9 alone in each sample set, achieving 67–80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glyCAns on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic CAncer could have important appliCAtions for improving the treatment and management of patients suffering from this disease.

  • IdentifiCAtion of blood-protein CArriers of the CA 19-9 Antigen and characterization of prevalence in pancreatic diseases
    Proteomics, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Mary C. Hurley, Philip C. Andrews, Karen L. Kaul, A. James Moser, Herbert J. Zeh, Randall E. Brand, Brian B. Haab
    Abstract:

    The current best serum marker for pancreatic CAncer, CA 19-9, detects a CArbohydrate Antigen on multiple protein CArriers. Better knowledge of the protein CArriers of the CA 19-9 Antigen in various disease states may lead to improved diagnostic tests. To identify proteins that CArry the CA 19-9 Antigen, we immunoprecipitated the CA 19-9 Antigen from pooled sera and identified the associated proteins using MS. Among the high-confidence identifiCAtions, we confirmed the presence of the CA 19-9 Antigen on Apolipoprotein B-100 by antibody arrays and Western blot and on kininogen, ARVCF, and Apolipoprotein E by antibody arrays. We characterized the frequency and levels of the CA 19-9 Antigen on the four proteins across various patient groups (pancreatic CAncer, pancreatitis, and healthy controls) using antibody arrays. Nearly, 10-25% of the subjects showed elevations of the Antigen on each protein, but the elevations were not associated with disease state or total CA 19-9 levels. These results contribute to our knowledge of the CArrier proteins of an important functional glyCAn and the rate at which the glyCAn is displayed. This work also demonstrates a strategy for using the complementary methods of MS and antibody microarrays to identify protein CArriers of glyCAns and assess the diagnostic value of measuring glyCAns on individual proteins.

  • Abstract 2216: Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 Antigen on specific protein CArriers
    Clinical Research, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Randall E. Brand, Michelle A. Anderson, Dean E. Brenner, Diane M. Simeone, Ziding Feng, Brian B. Haab
    Abstract:

    Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL The CA 19-9 assay detects a CArbohydrate Antigen on multiple protein CArriers, some of which may be preferential CArriers of the Antigen in CAncer. We tested the hypothesis that the measurement of the CA 19-9 Antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 Antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenoCArcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 420 individual samples. The measurement of the CA 19-9 Antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (79-88% sensitivity at 75% specificity), owing to diversity among patients in their CA 19-9 protein CArriers. However, a subset of CAncer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 Antigen specifiCAlly on the proteins MUC1, MUC5AC, or MUC16 in all three sample sets. By combining measurements of total CA 19-9 with CA 19-9 on these individual proteins, the sensitivity of CAncer detection was raised to 85-100% in the three sample sets, at a specificity of 75%. This finding demonstrates the potential value of measuring glyCAns on specific proteins for improving biomarker performance. Furthermore, the definition of subgroups of patients based on the protein CArriers of the CA 19-9 Antigen and other glyCAns will guide the further development of informative biomarker panels. Diagnostic tests with improved sensitivity for detecting pancreatic CAncer could have important appliCAtions for improving the treatment and management of patients suffering from this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the AmeriCAn Association for CAncer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; CAncer Res 2011;71(8 Suppl):Abstract nr 2216. doi:10.1158/1538-7445.AM2011-2216

Tingting Yue - One of the best experts on this subject based on the ideXlab platform.

  • Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 Antigen on specific protein CArriers.
    PloS one, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Karen L. Kaul, Herbert J. Zeh, Brian A Fallon, Michelle A. Anderson, Dean E. Brenner, A. James Moser
    Abstract:

    The CA 19-9 assay detects a CArbohydrate Antigen on multiple protein CArriers, some of which may be preferential CArriers of the Antigen in CAncer. We tested the hypothesis that the measurement of the CA 19-9 Antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 Antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenoCArcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 Antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage CAncer), owing to diversity among patients in their CA 19-9 protein CArriers. However, a subset of CAncer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 Antigen specifiCAlly on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of CAncer detection was improved relative to CA 19-9 alone in each sample set, achieving 67–80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glyCAns on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic CAncer could have important appliCAtions for improving the treatment and management of patients suffering from this disease.

  • IdentifiCAtion of blood-protein CArriers of the CA 19-9 Antigen and characterization of prevalence in pancreatic diseases
    Proteomics, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Mary C. Hurley, Philip C. Andrews, Karen L. Kaul, A. James Moser, Herbert J. Zeh, Randall E. Brand, Brian B. Haab
    Abstract:

    The current best serum marker for pancreatic CAncer, CA 19-9, detects a CArbohydrate Antigen on multiple protein CArriers. Better knowledge of the protein CArriers of the CA 19-9 Antigen in various disease states may lead to improved diagnostic tests. To identify proteins that CArry the CA 19-9 Antigen, we immunoprecipitated the CA 19-9 Antigen from pooled sera and identified the associated proteins using MS. Among the high-confidence identifiCAtions, we confirmed the presence of the CA 19-9 Antigen on Apolipoprotein B-100 by antibody arrays and Western blot and on kininogen, ARVCF, and Apolipoprotein E by antibody arrays. We characterized the frequency and levels of the CA 19-9 Antigen on the four proteins across various patient groups (pancreatic CAncer, pancreatitis, and healthy controls) using antibody arrays. Nearly, 10-25% of the subjects showed elevations of the Antigen on each protein, but the elevations were not associated with disease state or total CA 19-9 levels. These results contribute to our knowledge of the CArrier proteins of an important functional glyCAn and the rate at which the glyCAn is displayed. This work also demonstrates a strategy for using the complementary methods of MS and antibody microarrays to identify protein CArriers of glyCAns and assess the diagnostic value of measuring glyCAns on individual proteins.

  • Abstract 2216: Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 Antigen on specific protein CArriers
    Clinical Research, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Randall E. Brand, Michelle A. Anderson, Dean E. Brenner, Diane M. Simeone, Ziding Feng, Brian B. Haab
    Abstract:

    Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL The CA 19-9 assay detects a CArbohydrate Antigen on multiple protein CArriers, some of which may be preferential CArriers of the Antigen in CAncer. We tested the hypothesis that the measurement of the CA 19-9 Antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 Antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenoCArcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 420 individual samples. The measurement of the CA 19-9 Antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (79-88% sensitivity at 75% specificity), owing to diversity among patients in their CA 19-9 protein CArriers. However, a subset of CAncer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 Antigen specifiCAlly on the proteins MUC1, MUC5AC, or MUC16 in all three sample sets. By combining measurements of total CA 19-9 with CA 19-9 on these individual proteins, the sensitivity of CAncer detection was raised to 85-100% in the three sample sets, at a specificity of 75%. This finding demonstrates the potential value of measuring glyCAns on specific proteins for improving biomarker performance. Furthermore, the definition of subgroups of patients based on the protein CArriers of the CA 19-9 Antigen and other glyCAns will guide the further development of informative biomarker panels. Diagnostic tests with improved sensitivity for detecting pancreatic CAncer could have important appliCAtions for improving the treatment and management of patients suffering from this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the AmeriCAn Association for CAncer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; CAncer Res 2011;71(8 Suppl):Abstract nr 2216. doi:10.1158/1538-7445.AM2011-2216

  • Abstract 5567: Pancreatic disease-specific CArriers of the CA 19-9 Antigen identified by antibody microarrays and mass spectrometry
    Cancer Chemistry, 2010
    Co-Authors: Tingting Yue, Mary C. Hurley, Philip C. Andrews, Randel E. Brand, Brian B. Haab
    Abstract:

    Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Distinguishing patients with malignant pancreatic tumors from those with benign conditions is critiCAl for doctors to make proper treatment decisions. However, this process is usually costly and invasive due to the lack of a simple detection method such as a blood test. The current standard serologiCAl biomarker of pancreatic CAncer, the CA 19-9 Antigen, is not accurate enough for early diagnosis due to its ocCAsional elevation in benign pancreatic diseases. The CA 19-9 Antigen is a CArbohydrate epitope found on multiple protein CArriers. We sought to determine whether the protein CArriers of the CA 19-9 Antigen are different between benign and malignant pancreatic disease, and whether these differences could be harnessed to develop improved biomarkers. Two approaches were used to investigate this question. In the first, we used antibody microarrays to CApture multiple different mucins from the sera of early-stage pancreatic CAncer patients (n = 33), late-stage pancreatic CAncer patients (n = 17), pancreatitis patients (n = 38), and healthy control subjects (n = 20), and we probed the level of the CA 19-9 Antigen on the CAptured proteins using a monoclonal antibody. Pancreatic CAncer progression was associated with a shift in CA 19-9 CArriers from MUC16 to MUC1 and MUC5AC. Certain monoclonal antibodies CAptured glycoforms of MUC1 that predominantly CArried CA 19-9 in the CAncer patients. BeCAuse of that relationship, the detection of CA 19-9 on specific protein glycoforms improved the discrimination of CAncer from control subjects over total CA 19-9 (AUC= 0.93 vs. AUC=0.86. In the second approach, we immunoprecipitated CA19-9 CArrier proteins from pooled sera of late-stage CAncer, early-stage CAncer, pancreatitis, and control subjects, followed by deglycosylation and mass spectrometry (MALDI/TOF/TOF). Several proteins were identified in the sera of the CAncer patients but not in the sera of pancreatitis or control subjects, indiCAting the possible identifiCAtion of state-specific CArriers of CA 19-9. Ongoing studies are aimed at verifying these identifiCAtions and testing performance as biomarkers of pancreatic CAncer. These findings may lead to more accurate methods of discriminating benign from malignant pancreatic disease, which would improve the ability to render proper CAre to patients at the earliest possible stages. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the AmeriCAn Association for CAncer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; CAncer Res 2010;70(8 Suppl):Abstract nr 5567.

A. James Moser - One of the best experts on this subject based on the ideXlab platform.

  • Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 Antigen on specific protein CArriers.
    PloS one, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Karen L. Kaul, Herbert J. Zeh, Brian A Fallon, Michelle A. Anderson, Dean E. Brenner, A. James Moser
    Abstract:

    The CA 19-9 assay detects a CArbohydrate Antigen on multiple protein CArriers, some of which may be preferential CArriers of the Antigen in CAncer. We tested the hypothesis that the measurement of the CA 19-9 Antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 Antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenoCArcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 Antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage CAncer), owing to diversity among patients in their CA 19-9 protein CArriers. However, a subset of CAncer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 Antigen specifiCAlly on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of CAncer detection was improved relative to CA 19-9 alone in each sample set, achieving 67–80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glyCAns on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic CAncer could have important appliCAtions for improving the treatment and management of patients suffering from this disease.

  • IdentifiCAtion of blood-protein CArriers of the CA 19-9 Antigen and characterization of prevalence in pancreatic diseases
    Proteomics, 2011
    Co-Authors: Tingting Yue, Katie Partyka, Kevin A. Maupin, Mary C. Hurley, Philip C. Andrews, Karen L. Kaul, A. James Moser, Herbert J. Zeh, Randall E. Brand, Brian B. Haab
    Abstract:

    The current best serum marker for pancreatic CAncer, CA 19-9, detects a CArbohydrate Antigen on multiple protein CArriers. Better knowledge of the protein CArriers of the CA 19-9 Antigen in various disease states may lead to improved diagnostic tests. To identify proteins that CArry the CA 19-9 Antigen, we immunoprecipitated the CA 19-9 Antigen from pooled sera and identified the associated proteins using MS. Among the high-confidence identifiCAtions, we confirmed the presence of the CA 19-9 Antigen on Apolipoprotein B-100 by antibody arrays and Western blot and on kininogen, ARVCF, and Apolipoprotein E by antibody arrays. We characterized the frequency and levels of the CA 19-9 Antigen on the four proteins across various patient groups (pancreatic CAncer, pancreatitis, and healthy controls) using antibody arrays. Nearly, 10-25% of the subjects showed elevations of the Antigen on each protein, but the elevations were not associated with disease state or total CA 19-9 levels. These results contribute to our knowledge of the CArrier proteins of an important functional glyCAn and the rate at which the glyCAn is displayed. This work also demonstrates a strategy for using the complementary methods of MS and antibody microarrays to identify protein CArriers of glyCAns and assess the diagnostic value of measuring glyCAns on individual proteins.