Glycans Related to the CA19-9 Antigen Are Increased in Distinct Subsets of Pancreatic Cancers and Improve Diagnostic Accuracy Over CA19-9

Tang, Huiyuan; Partyka, Katie; Hsueh, Peter; Sinha, Jessica; Kletter, Doron; Zeh, Herbert J.; Huang, Ying; Brand, Randall E.; Haab, Brian B.

doi:10.1016/j.jcmgh.2015.12.003

Cited by 37 publications

(36 citation statements)

References 38 publications

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“…In fact, a relevant issue to be addressed concerns the potential expression of sLe x in conjunction or alternative to CA19.9. Recently, it was proposed that CA19.9-negative cancer patients may be monitored through circulating sLe x [134], and the expression of sLe x in distinct glycans appears to be independent of that of sLe a , potentially improving the diagnostic accuracy over CA19.9 [135]. The expression of sLe x on plasma protein seems to be actually associated with gastrointestinal cancers, as above reported [96].…”

Section: Role In Diagnosismentioning

confidence: 91%

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

Trinchera

Aronica

Dall’Olio

2017

Biology

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The tetrasaccharide structures Siaα2,3Galβ1,3(Fucα1,4)GlcNAc and Siaα2,3Galβ1,4(Fucα1,3)GlcNAc constitute the epitopes of the carbohydrate antigens sialyl-Lewis a (sLea) and sialyl-Lewis x (sLex), respectively, and are the minimal requirement for selectin binding to their counter-receptors. Interaction of sLex expressed on the cell surface of leucocytes with E-selectin on endothelial cells allows their arrest and promotes their extravasation. Similarly, the rolling of cancer cells ectopically expressing the selectin ligands on endothelial cells is potentially a crucial step favoring the metastatic process. In this review, we focus on the biosynthetic steps giving rise to selectin ligand expression in cell lines and native tissues of gastrointestinal origin, trying to understand whether and how they are deregulated in cancer. We also discuss the use of such molecules in the diagnosis of gastrointestinal cancers, particularly in light of recent data questioning the ability of colon cancers to express sLea and the possible use of circulating sLex in the early detection of pancreatic cancer. Finally, we reviewed the data dealing with the mechanisms that link selectin ligand expression in gastrointestinal cells to cancer malignancy. This promising research field seems to require additional data on native patient tissues to reach more definitive conclusions.

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Section: Role In Diagnosismentioning

confidence: 91%

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

Trinchera

Aronica

Dall’Olio

2017

Biology

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“…Sialyl-Le x/a , which are expressed either protein- or lipid-bound on the cell surface, have their expression increased in different types of cancer, including gastric, colorectal, oral squamous cell, and pancreatic cancer [141-144]. During the metastasis process, they act as carbohydrate ligands for E-selectin-mediated cancer cell adhesion [145].…”

Section: Hypoxia Changes Membrane Glycoconjugates In Tumor Cellsmentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

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“…The sialy-Lewis X glycan showed elevations in 30%-50% of the patients with low CA19-9 but also showed elevations in about 10% of patients with benign pancreatic diseases. Another glycan, referred to as sTRA, was elevated in up to half of the patients with low CA19-9, with very low false-positive rates (7). In subsequent research, we found that the cells producing sTRA are different in location, morphologies, and molecular characteristics than the cells producing CA19-9 (8).…”

Section: Introductionmentioning

confidence: 74%

The sTRA Plasma Biomarker: Blinded Validation of Improved Accuracy Over CA19-9 in Pancreatic Cancer Diagnosis

Staal

Liu

Barnett

et al. 2019

Clinical Cancer Research

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Purpose: The CA19-9 biomarker is elevated in a substantial group of patients with pancreatic ductal adenocarcinoma (PDAC), but not enough to be reliable for the detection or diagnosis of the disease. We hypothesized that a glycan called sTRA (sialylated tumor-related antigen) is a biomarker for PDAC that improves upon CA19-9. Experimental Design: We examined sTRA and CA19-9 expression and secretion in panels of cell lines, patient-derived xenografts, and primary tumors. We developed candidate biomarkers from sTRA and CA19-9 in a training set of 147 plasma samples and used the panels to make case-control calls, based on predetermined thresholds, in a 50-sample validation set and a blinded, 147-sample test set. Results: The sTRA glycan was produced and secreted by pancreatic tumors and models that did not produce and secrete CA19-9. Two biomarker panels improved upon CA19-9 in the training set, one optimized for specificity, which included CA19-9 and 2 versions of the sTRA assay, and another optimized for sensitivity, which included 2 sTRA assays. Both panels achieved statistical improvement (P < 0.001) over CA19-9 in the validation set, and the specificity-optimized panel achieved statistical improvement (P < 0.001) in the blinded set: 95% specificity and 54% sensitivity (75% accuracy), compared with 97%/30% (65% accuracy). Unblinding produced further improvements and revealed independent, complementary contributions from each marker. Conclusions: sTRA is a validated serological biomarker of PDAC that yields improved performance over CA19-9. The new panels may enable surveillance for PDAC among people with elevated risk, or improved differential diagnosis among patients with suspected pancreatic cancer.

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Glycans Related to the CA19-9 Antigen Are Increased in Distinct Subsets of Pancreatic Cancers and Improve Diagnostic Accuracy Over CA19-9

Cited by 37 publications

References 38 publications

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

The sTRA Plasma Biomarker: Blinded Validation of Improved Accuracy Over CA19-9 in Pancreatic Cancer Diagnosis

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