Heterogeneity of glycan biomarker clusters as an indicator of recurrence in pancreatic cancer.

Abstract

Introduction

Outcomes following tumor resection vary dramatically among patients with pancreatic ductal adenocarcinoma (PDAC). A challenge in defining predictive biomarkers is to discern within the complex tumor tissue the specific subpopulations and relationships that drive recurrence. Multiplexed immunofluorescence is valuable for such studies when supplied with markers of relevant subpopulations and analysis methods to sort out the intra-tumor relationships that are informative of tumor behavior. We hypothesized that the glycan biomarkers CA19-9 and STRA, which detect separate subpopulations of cancer cells, define intra-tumoral features associated with recurrence.

Methods

We probed this question using automated signal thresholding and spatial cluster analysis applied to the immunofluorescence images of the STRA and CA19-9 glycan biomarkers in whole-block sections of PDAC tumors collected from curative resections.

Results

The tumors (N = 22) displayed extreme diversity between them in the amounts of the glycans and in the levels of spatial clustering, but neither the amounts nor the clusters of the individual and combined glycans associated with recurrence. The combined glycans, however, marked divergent types of spatial clusters, alternatively only STRA, only CA19-9, or both. The co-occurrence of more than one cluster type within a tumor associated significantly with disease recurrence, in contrast to the independent occurrence of each type of cluster. In addition, intra-tumoral regions with heterogeneity in biomarker clusters spatially aligned with pathology-confirmed cancer cells, whereas regions with homogeneous biomarker clusters aligned with various non-cancer cells.

Conclusion

Thus, the STRA and CA19-9 glycans are markers of distinct and co-occurring subpopulations of cancer cells that in combination are associated with recurrence. Furthermore, automated signal thresholding and spatial clustering provides a tool for quantifying intra-tumoral subpopulations that are informative of outcome.

Department

Description

Provenance

Subjects

biomarkers, digital pathology, glycans, multiplexed immunofluorescence, pancreatic cancer, recurrence

Citation

Published Version (Please cite this version)

10.3389/fonc.2023.1135405

Publication Info

Wisniewski, Luke, Samuel Braak, Zachary Klamer, ChongFeng Gao, Chanjuan Shi, Peter Allen and Brian B Haab (2023). Heterogeneity of glycan biomarker clusters as an indicator of recurrence in pancreatic cancer. Frontiers in oncology, 13. p. 1135405. 10.3389/fonc.2023.1135405 Retrieved from https://hdl.handle.net/10161/27379.

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Scholars@Duke

Shi

Chanjuan Shi

Professor of Pathology

Dr. Shi is a gastrointestinal (GI)/liver pathologist. Her particular areas of interest are GI and pancreatic neuroendocrine tumors and pancreatic pathology. Her research interests include 1)  Pathobiology of GI and pancreatic neuroendocrine tumors and 2) Identification of diagnostic, prognostic and therapeutic biomarkers for colorectal and pancreatic cancers


Allen

Peter Allen

David C. Sabiston, Jr. Distinguished Professor of Surgery

I am a Surgical Oncologist with clinical and research training in pancreatic and hepatobiliary malignancy.  In 2018, I joined Duke University as the Chief of Surgical Oncology, and the Chief of Surgery in the Duke Cancer Institute.  Previously, I led the clinical and research efforts regarding pancreatic neoplasia within the Department of Surgery at Memorial Sloan Kettering Cancer Center, and served as the Associate Director for Clinical Programs within the David Rubenstein Center for Pancreatic Cancer Research. I also held the Murray F. Brennan endowed Chair in Surgery. 

Over the previous ten years, I have been interested in the progression of pancreatic precursor lesions called intraductal papillary mucinous neoplasms (IPMN).  These cystic precursor lesions of the pancreas present an opportunity for to both study cancer progression, and potentially prevent the development of this lethal malignancy.  My research has focused on biomarker development to identify high-risk IPMN as well as studies evaluating the cause of this disease process.  I have successfully completed phase II and phase III clinical trials in patients with pancreatic cancer and IPMN, and am currently the PI of a first-in-human multi-center randomized chemoprevention trial for pancreatic cancer that is targeting patients with high-risk IPMN.

My laboratory includes both pre and postdoctoral trainees, and they play a critical role in the development of our pancreatic cancer prevention program. 


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