Enhanced Discrimination of Malignant from Benign Pancreatic Disease by Measuring the CA 19-9 Antigen on Specific Protein Carriers

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.

Specific Glycoforms of MUC5AC and Endorepellin Accurately Distinguish Mucinous from Nonmucinous Pancreatic Cysts

“…A glycoform of MUC5AC, one that binds the lectin wheat germ agglutinin (WGA), was almost exclusively found in the mucinous cysts and was a better biomarker than the MUC5AC protein measured over all glycoforms. Furthermore, the glycosylation patterns in pancreatic cysts were different from those we found in pancreatic ductal adenocarcinomas (21,22).…”

Serum Tumor Marker Levels in Rheumatoid Arthritis

“…Carbohydrate antigen 19-9 (CA 19-9) is a tumor associated oligosaccharide oncofetal antigen which is closely related to the sialylated Lewis blood group antigen (sLea). High serum levels are commonly associated with pancreatic cancer or cholangiocarcinoma as well as many other cancer types (7). sLea plays a pivotal role in adhesion of leukocytes to the inflamed joint by acting as a ligand for various cell adhesion molecules.…”

“…CA 19.9 antigen is commonly overexpressed in pancreatic cancer cells however it is not specific to pancreas cancer. Like other antigens high serum levels can be found in various other cancer types and inflammatory conditions such as hepatitis (7). Carcinoembryonic antigen (CEA) is an oncofetal antigen which is normally expressed in fetal digestive tract.…”

Requests for Tumor Marker Tests in Turkey Without Indications and Frequency of Elevation in Benign Conditions

“…For example, CA 19-9 is known to be elevated in gastrointestinal tumors and has a sensitivity of 79-81% and a specificity of 82-90% in patients with asymptomatic pancreatic cancer (Ballehaninna and Chamberlain, 2011). It may be increased in benign cases such as acute cholecystitis, biliary obstruction and liver disease as well (Dogan et al, 2011;Yue et al, 2011). Even heavy tea consumption can lead to elevated serum CA19-9 levels (Howaizi et al, 2003).…”