Differential expression of CD175 and CA19-9 in pancreatic adenocarcinoma

Abstract Alterations in protein glycosylation are observed in many solid tumor types leading to formation of tumor-associated carbohydrate antigens (TACAs). The most common TACA is the Tn antigen (CD175), which is a mucin-type O-GalNAc-Ser/Thr/Tyr glycan in membrane and secreted glycoproteins. In ad...

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Main Authors: Jane J. Cheng, Yasuyuki Matsumoto, Gabrielle E. Dombek, Kathryn A. Stackhouse, Ana Sofia Ore, Jonathan N. Glickman, Jamie Heimburg-Molinaro, Richard D. Cummings
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86988-8
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author Jane J. Cheng
Yasuyuki Matsumoto
Gabrielle E. Dombek
Kathryn A. Stackhouse
Ana Sofia Ore
Jonathan N. Glickman
Jamie Heimburg-Molinaro
Richard D. Cummings
author_facet Jane J. Cheng
Yasuyuki Matsumoto
Gabrielle E. Dombek
Kathryn A. Stackhouse
Ana Sofia Ore
Jonathan N. Glickman
Jamie Heimburg-Molinaro
Richard D. Cummings
author_sort Jane J. Cheng
collection DOAJ
description Abstract Alterations in protein glycosylation are observed in many solid tumor types leading to formation of tumor-associated carbohydrate antigens (TACAs). The most common TACA is the Tn antigen (CD175), which is a mucin-type O-GalNAc-Ser/Thr/Tyr glycan in membrane and secreted glycoproteins. In addition, two other TACAs are CA19-9 (sialyl-Lewis a), which is used as a prognostic serum marker for pancreatic cancer, and its isomer sialyl-Lewis x (SLex, CD15s), which is overexpressed in many cancer types and associated with metastasis. While CD175 and other TACAs may be expressed by many human carcinomas, little is known about their differential expression patterns in tumors, thus limiting their use as tissue biomarkers or therapeutic targets. Here we address the clinicopathological relevance of the expression of CA19-9, CD15s, and CD175 in pancreatic ductal adenocarcinoma (PDAC) tissues. Semi-quantitative IHC staining with well-defined monoclonal antibodies demonstrates that CD175 is expressed in all PDAC specimens analyzed. Unexpectedly, however, these TACAs are differentially expressed within PDAC specimens and their glycoproteins, but not significantly expressed in adjacent normal tissues. These data provide avenues for novel therapeutic approaches that could combine CD175- and CA19-9-targeting therapies for PDAC patients.
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spelling doaj-art-5a613fbe105c41919c1f376a24bf20172025-02-09T12:37:25ZengNature PortfolioScientific Reports2045-23222025-02-0115111110.1038/s41598-025-86988-8Differential expression of CD175 and CA19-9 in pancreatic adenocarcinomaJane J. Cheng0Yasuyuki Matsumoto1Gabrielle E. Dombek2Kathryn A. Stackhouse3Ana Sofia Ore4Jonathan N. Glickman5Jamie Heimburg-Molinaro6Richard D. Cummings7Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical SchoolAbstract Alterations in protein glycosylation are observed in many solid tumor types leading to formation of tumor-associated carbohydrate antigens (TACAs). The most common TACA is the Tn antigen (CD175), which is a mucin-type O-GalNAc-Ser/Thr/Tyr glycan in membrane and secreted glycoproteins. In addition, two other TACAs are CA19-9 (sialyl-Lewis a), which is used as a prognostic serum marker for pancreatic cancer, and its isomer sialyl-Lewis x (SLex, CD15s), which is overexpressed in many cancer types and associated with metastasis. While CD175 and other TACAs may be expressed by many human carcinomas, little is known about their differential expression patterns in tumors, thus limiting their use as tissue biomarkers or therapeutic targets. Here we address the clinicopathological relevance of the expression of CA19-9, CD15s, and CD175 in pancreatic ductal adenocarcinoma (PDAC) tissues. Semi-quantitative IHC staining with well-defined monoclonal antibodies demonstrates that CD175 is expressed in all PDAC specimens analyzed. Unexpectedly, however, these TACAs are differentially expressed within PDAC specimens and their glycoproteins, but not significantly expressed in adjacent normal tissues. These data provide avenues for novel therapeutic approaches that could combine CD175- and CA19-9-targeting therapies for PDAC patients.https://doi.org/10.1038/s41598-025-86988-8Tumor-associated carbohydrate antigens (TACAs)CD175Sialyl-Lewis a (CA19-9)CA19-9Sialyl-Lewis x (CD15s)Pancreatic ductal adenocarcinoma (PDAC)
spellingShingle Jane J. Cheng
Yasuyuki Matsumoto
Gabrielle E. Dombek
Kathryn A. Stackhouse
Ana Sofia Ore
Jonathan N. Glickman
Jamie Heimburg-Molinaro
Richard D. Cummings
Differential expression of CD175 and CA19-9 in pancreatic adenocarcinoma
Scientific Reports
Tumor-associated carbohydrate antigens (TACAs)
CD175
Sialyl-Lewis a (CA19-9)
CA19-9
Sialyl-Lewis x (CD15s)
Pancreatic ductal adenocarcinoma (PDAC)
title Differential expression of CD175 and CA19-9 in pancreatic adenocarcinoma
title_full Differential expression of CD175 and CA19-9 in pancreatic adenocarcinoma
title_fullStr Differential expression of CD175 and CA19-9 in pancreatic adenocarcinoma
title_full_unstemmed Differential expression of CD175 and CA19-9 in pancreatic adenocarcinoma
title_short Differential expression of CD175 and CA19-9 in pancreatic adenocarcinoma
title_sort differential expression of cd175 and ca19 9 in pancreatic adenocarcinoma
topic Tumor-associated carbohydrate antigens (TACAs)
CD175
Sialyl-Lewis a (CA19-9)
CA19-9
Sialyl-Lewis x (CD15s)
Pancreatic ductal adenocarcinoma (PDAC)
url https://doi.org/10.1038/s41598-025-86988-8
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