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Definitive Characterization of CA 19-9 in Resectable Pancreatic Cancer Using a Reference Set of Serum and Plasma Specimens.

Haab BB, Huang Y, Balasenthil S, Partyka K, Tang H, Anderson M, Allen P, Sasson A, Zeh H, Kaul K, Kletter D, Ge S, Bern M, Kwon R, Blasutig I, Srivastava S, Frazier ML, Sen S, Hollingsworth MA, Rinaudo JA, Killary AM, Brand RE - PLoS ONE (2015)

Bottom Line: We gained additional information about the biomarker by comparing two distinct assays.The two CA 9-9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis.Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19-9 data presented here will be useful for benchmarking and for exploring relationships to CA 19-9.

View Article: PubMed Central - PubMed

Affiliation: Van Andel Research Institute, Grand Rapids, MI, United States of America.

ABSTRACT
The validation of candidate biomarkers often is hampered by the lack of a reliable means of assessing and comparing performance. We present here a reference set of serum and plasma samples to facilitate the validation of biomarkers for resectable pancreatic cancer. The reference set includes a large cohort of stage I-II pancreatic cancer patients, recruited from 5 different institutions, and relevant control groups. We characterized the performance of the current best serological biomarker for pancreatic cancer, CA 19-9, using plasma samples from the reference set to provide a benchmark for future biomarker studies and to further our knowledge of CA 19-9 in early-stage pancreatic cancer and the control groups. CA 19-9 distinguished pancreatic cancers from the healthy and chronic pancreatitis groups with an average sensitivity and specificity of 70-74%, similar to previous studies using all stages of pancreatic cancer. Chronic pancreatitis patients did not show CA 19-9 elevations, but patients with benign biliary obstruction had elevations nearly as high as the cancer patients. We gained additional information about the biomarker by comparing two distinct assays. The two CA 9-9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis. Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19-9 data presented here will be useful for benchmarking and for exploring relationships to CA 19-9.

No MeSH data available.


Related in: MedlinePlus

Differentiating pancreatic cancer from control subjects by two different CA 19–9 assays.A) CA 19–9 levels in each group. We present the log-transformed values to better visualize all ranges of the values. The boxes indicate the quartiles of the distributions, the horizontal lines in the boxes indicate the medians, and the dashed lines give the ranges, with individual outliers indicated by the circles. A1, Assay 1; A2, Assay 2. B-D) Receiver-operator-characteristic (ROC) curves comparing all pancreatic cancer patients to the indicated control groups. The legends specify the area-under-the-curves (AUCs) for each assay, with the ranges of the 95% confidence intervals.
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pone.0139049.g001: Differentiating pancreatic cancer from control subjects by two different CA 19–9 assays.A) CA 19–9 levels in each group. We present the log-transformed values to better visualize all ranges of the values. The boxes indicate the quartiles of the distributions, the horizontal lines in the boxes indicate the medians, and the dashed lines give the ranges, with individual outliers indicated by the circles. A1, Assay 1; A2, Assay 2. B-D) Receiver-operator-characteristic (ROC) curves comparing all pancreatic cancer patients to the indicated control groups. The legends specify the area-under-the-curves (AUCs) for each assay, with the ranges of the 95% confidence intervals.

Mentions: We first examined the distributions of the values for each of the assays in the various patient groups (Fig 1A). The healthy subjects and chronic pancreatitis patients had the lowest levels; benign biliary obstruction patients had significantly higher levels (p-value is less than 0.0001 and equal to 0.006 by Wilcoxon Rank Sum test, relative to healthy subjects for Assay 1 and 2 respectively); and cancer patients had the highest levels (p<0.0001 relative to healthy subjects based on either t-test or Wilcoxon Rank Sum test for each assay). The two assays showed equivalent trends. Detailed results about the geometric means of the individual assays and their 95% confidence intervals are presented in Table C in S3 File, and the p-values for the comparisons between patient groups are presented in Table D in S3 File.


Definitive Characterization of CA 19-9 in Resectable Pancreatic Cancer Using a Reference Set of Serum and Plasma Specimens.

Haab BB, Huang Y, Balasenthil S, Partyka K, Tang H, Anderson M, Allen P, Sasson A, Zeh H, Kaul K, Kletter D, Ge S, Bern M, Kwon R, Blasutig I, Srivastava S, Frazier ML, Sen S, Hollingsworth MA, Rinaudo JA, Killary AM, Brand RE - PLoS ONE (2015)

Differentiating pancreatic cancer from control subjects by two different CA 19–9 assays.A) CA 19–9 levels in each group. We present the log-transformed values to better visualize all ranges of the values. The boxes indicate the quartiles of the distributions, the horizontal lines in the boxes indicate the medians, and the dashed lines give the ranges, with individual outliers indicated by the circles. A1, Assay 1; A2, Assay 2. B-D) Receiver-operator-characteristic (ROC) curves comparing all pancreatic cancer patients to the indicated control groups. The legends specify the area-under-the-curves (AUCs) for each assay, with the ranges of the 95% confidence intervals.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592020&req=5

pone.0139049.g001: Differentiating pancreatic cancer from control subjects by two different CA 19–9 assays.A) CA 19–9 levels in each group. We present the log-transformed values to better visualize all ranges of the values. The boxes indicate the quartiles of the distributions, the horizontal lines in the boxes indicate the medians, and the dashed lines give the ranges, with individual outliers indicated by the circles. A1, Assay 1; A2, Assay 2. B-D) Receiver-operator-characteristic (ROC) curves comparing all pancreatic cancer patients to the indicated control groups. The legends specify the area-under-the-curves (AUCs) for each assay, with the ranges of the 95% confidence intervals.
Mentions: We first examined the distributions of the values for each of the assays in the various patient groups (Fig 1A). The healthy subjects and chronic pancreatitis patients had the lowest levels; benign biliary obstruction patients had significantly higher levels (p-value is less than 0.0001 and equal to 0.006 by Wilcoxon Rank Sum test, relative to healthy subjects for Assay 1 and 2 respectively); and cancer patients had the highest levels (p<0.0001 relative to healthy subjects based on either t-test or Wilcoxon Rank Sum test for each assay). The two assays showed equivalent trends. Detailed results about the geometric means of the individual assays and their 95% confidence intervals are presented in Table C in S3 File, and the p-values for the comparisons between patient groups are presented in Table D in S3 File.

Bottom Line: We gained additional information about the biomarker by comparing two distinct assays.The two CA 9-9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis.Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19-9 data presented here will be useful for benchmarking and for exploring relationships to CA 19-9.

View Article: PubMed Central - PubMed

Affiliation: Van Andel Research Institute, Grand Rapids, MI, United States of America.

ABSTRACT
The validation of candidate biomarkers often is hampered by the lack of a reliable means of assessing and comparing performance. We present here a reference set of serum and plasma samples to facilitate the validation of biomarkers for resectable pancreatic cancer. The reference set includes a large cohort of stage I-II pancreatic cancer patients, recruited from 5 different institutions, and relevant control groups. We characterized the performance of the current best serological biomarker for pancreatic cancer, CA 19-9, using plasma samples from the reference set to provide a benchmark for future biomarker studies and to further our knowledge of CA 19-9 in early-stage pancreatic cancer and the control groups. CA 19-9 distinguished pancreatic cancers from the healthy and chronic pancreatitis groups with an average sensitivity and specificity of 70-74%, similar to previous studies using all stages of pancreatic cancer. Chronic pancreatitis patients did not show CA 19-9 elevations, but patients with benign biliary obstruction had elevations nearly as high as the cancer patients. We gained additional information about the biomarker by comparing two distinct assays. The two CA 9-9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis. Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19-9 data presented here will be useful for benchmarking and for exploring relationships to CA 19-9.

No MeSH data available.


Related in: MedlinePlus