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2016 Scientific Report

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Other research is aimed at further improving the biomarker<br />

tests. The results so far suggest that each individual<br />

biomarker arises from a distinct subpopulation of cancer<br />

patients and from a characteristic cell type. This finding is<br />

important because the biomarkers may reveal differences<br />

between subgroups of tumors—a possibility we are<br />

exploring in the research described below. For the purpose<br />

of improving our blood tests, determining the characteristics<br />

of the cells that produce each biomarker, as well as of the<br />

cells that do not produce any of our biomarkers, will help to<br />

optimize a blood test to accurately identify cancers across<br />

the entire spectrum of patients.<br />

The ultimate goal is to get the new tests established in<br />

clinical laboratories in order to benefit patients. To that<br />

end, we are working with industry partners to transfer our<br />

biomarker assays to the clinical laboratory setting and to<br />

begin analyzing patient samples received consecutively<br />

from clinical sites. If we have good results, we hope to<br />

initiate clinical trials for the diagnosis of pancreatic cancer<br />

and, eventually, for evaluations of surveillance among<br />

people at elevated risk for pancreatic cancer.<br />

Better treatment through subtyping<br />

Pancreatic cancer characteristics, such as the cell types<br />

within the tumor, the amount of metastasis, the responses<br />

to treatments, and overall outcomes, vary greatly among<br />

patients. So far, identifying the underlying causes of such<br />

differences and predicting the behavior of individual tumors<br />

have not been possible. If we could determine what drives<br />

the differences between the tumors or identify molecules<br />

that help predict the behavior of each tumor, we could<br />

establish better treatment plans for each patient or<br />

determine the drugs that work best against each subtype.<br />

Our research is revealing major groupings of tumors<br />

based on the carbohydrates on the surface of, and in<br />

the secretions from, cancer cells. The carbohydrates are<br />

related to the CA19-9 antigen and have distinct biological<br />

functions. In current research we want to determine the<br />

molecular nature of the subgroups of cells and whether<br />

the subgroups have different levels of aggressiveness or<br />

different responses to particular drugs. We are using new<br />

approaches for measuring carbohydrates and proteins<br />

in tumor tissue, and we are employing powerful new<br />

software—introduced in our recent publication in Analytical<br />

Chemistry—to examine the cell types that produce<br />

each carbohydrate-based biomarker. We are using that<br />

information to evaluate whether certain types of cells<br />

predict clinical behavior. As advances and new options<br />

in treatments become available, this type of research is<br />

increasingly important for guiding clinical decisions. We<br />

are working closely with our physician collaborators to<br />

evaluate on a case-by-case basis the value of the molecular<br />

information and to guide our research toward improving the<br />

tests. Ultimately, physicians could use the molecular tests<br />

on material from biopsies, surgical resections, or blood<br />

samples.<br />

RECENT PUBLICATIONS<br />

Ensink, Elliot, Jessica Sinha, Arkadeep Sinha, Huiyuan Tang, Heather M. Calderone, Galen Hostetter, Jordan Winter, David<br />

Cherba, Randall E. Brand, et al. 2015. Segment and fit thresholding: a new method for image analysis applied to microarray and<br />

immunofluorescence data. Analytical Chemistry 87(19): 9715–9721.<br />

Singh, Sudhir, Kuntal Pal, Jessica Yadav, Huiyuan Tang, Katie Partyka, Doron Kletter, Peter Hsueh, Elliot Ensink, Birendra KC, et<br />

al. 2015. Upregulation of glycans containing 3' fucose in a subset of pancreatic cancers uncovered using fusion-tagged lectins.<br />

Journal of Proteome Research 14(6): 2594–2605.<br />

Tang, Huiyuan, Sudhir Singh, Katie Partyka, Doron Kletter, Peter Hsueh, Jessica Yadav, Elliot Ensink, Marshall Bern, Galen<br />

Hostetter, et al. 2015. Glycan motif profiling reveals plasma sialyl-Lewis X elevations in pancreatic cancers that are negative for<br />

CA19-9. Molecular & Cellular Proteomics 14(5): 1323–1333.<br />

10<br />

Van Andel Research Institute | <strong>Scientific</strong> <strong>Report</strong>

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