Comprehensive analysis of UPK3B as a marker for prognosis and immunity in pancreatic adenocarcinoma

Abstract The low immunogenicity of pancreatic cancer inhibits effective antitumor immune responses, primarily due to the immune evasion mediated by low expression of the major histocompatibility complex (MHC). Through comprehensive analysis, our study identifies UPK3B as a gene closely associated wi...

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Main Authors: Ziying Jian, Tao Pan, Renjie Li, Weiyu Zhang, Tao Cheng, Hanzhe Zhang, Jialin Song, Naipeng Shi, Zhiheng Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-97213-x
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author Ziying Jian
Tao Pan
Renjie Li
Weiyu Zhang
Tao Cheng
Hanzhe Zhang
Jialin Song
Naipeng Shi
Zhiheng Zhang
author_facet Ziying Jian
Tao Pan
Renjie Li
Weiyu Zhang
Tao Cheng
Hanzhe Zhang
Jialin Song
Naipeng Shi
Zhiheng Zhang
author_sort Ziying Jian
collection DOAJ
description Abstract The low immunogenicity of pancreatic cancer inhibits effective antitumor immune responses, primarily due to the immune evasion mediated by low expression of the major histocompatibility complex (MHC). Through comprehensive analysis, our study identifies UPK3B as a gene closely associated with low MHC expression and low immunogenicity in pancreatic cancer. UPK3B has been reported as a marker of primary mesothelial cells, mature epicardium and promotes extracellular matrix signaling. However, the role of UPK3B in pancreatic cancer remain unclear. We found that UPK3B is highly predictive of overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) and is significantly related to clinical features, immune cell infiltration, and response to immune checkpoint inhibitor (ICI) therapy. Gene enrichment analysis revealed significant downregulation of immune regulatory and BCR signaling pathways in the UPK3B high-expression group. Additionally, UPK3B is positively correlated with immunosuppressive cells, suggesting that high UPK3B expression may inhibit antitumor immune responses by promoting low MHC expression. UPK3B is also positively correlated with immune checkpoints, indicating that tumors with high UPK3B expression may not benefit from ICI therapy. Therefore, UPK3B may serve as a novel biomarker and therapeutic target for pancreatic cancer.
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spelling doaj-art-d7d888f667c646bf8e294b048e7f7cfa2025-08-20T03:06:57ZengNature PortfolioScientific Reports2045-23222025-04-0115111410.1038/s41598-025-97213-xComprehensive analysis of UPK3B as a marker for prognosis and immunity in pancreatic adenocarcinomaZiying Jian0Tao Pan1Renjie Li2Weiyu Zhang3Tao Cheng4Hanzhe Zhang5Jialin Song6Naipeng Shi7Zhiheng Zhang8Department of Hematology, Zhong da Hospital of Southeast UniversityDepartment of Radiology, Center of Interventional Radiology and Vascular Surgery, Medical School, Zhongda Hospital, Southeast UniversitySchool of Medicine, Southeast UniversityDepartment of General Surgery, Zhongda Hospital of Southeast UniversityDepartment of General Surgery, Zhongda Hospital of Southeast UniversitySchool of Medicine, Southeast UniversitySchool of Medicine, Southeast UniversityDepartment of Urology, Northern Jiangsu People’s HospitalDivision of Hepatobiliary and Transplantation Surgery, Department of General Surgery, The Affiliated Hospital of Nanjing University Medical SchoolAbstract The low immunogenicity of pancreatic cancer inhibits effective antitumor immune responses, primarily due to the immune evasion mediated by low expression of the major histocompatibility complex (MHC). Through comprehensive analysis, our study identifies UPK3B as a gene closely associated with low MHC expression and low immunogenicity in pancreatic cancer. UPK3B has been reported as a marker of primary mesothelial cells, mature epicardium and promotes extracellular matrix signaling. However, the role of UPK3B in pancreatic cancer remain unclear. We found that UPK3B is highly predictive of overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) and is significantly related to clinical features, immune cell infiltration, and response to immune checkpoint inhibitor (ICI) therapy. Gene enrichment analysis revealed significant downregulation of immune regulatory and BCR signaling pathways in the UPK3B high-expression group. Additionally, UPK3B is positively correlated with immunosuppressive cells, suggesting that high UPK3B expression may inhibit antitumor immune responses by promoting low MHC expression. UPK3B is also positively correlated with immune checkpoints, indicating that tumors with high UPK3B expression may not benefit from ICI therapy. Therefore, UPK3B may serve as a novel biomarker and therapeutic target for pancreatic cancer.https://doi.org/10.1038/s41598-025-97213-xPancreatic CancerImmunosuppressionMHCPrognosisBiomarker
spellingShingle Ziying Jian
Tao Pan
Renjie Li
Weiyu Zhang
Tao Cheng
Hanzhe Zhang
Jialin Song
Naipeng Shi
Zhiheng Zhang
Comprehensive analysis of UPK3B as a marker for prognosis and immunity in pancreatic adenocarcinoma
Scientific Reports
Pancreatic Cancer
Immunosuppression
MHC
Prognosis
Biomarker
title Comprehensive analysis of UPK3B as a marker for prognosis and immunity in pancreatic adenocarcinoma
title_full Comprehensive analysis of UPK3B as a marker for prognosis and immunity in pancreatic adenocarcinoma
title_fullStr Comprehensive analysis of UPK3B as a marker for prognosis and immunity in pancreatic adenocarcinoma
title_full_unstemmed Comprehensive analysis of UPK3B as a marker for prognosis and immunity in pancreatic adenocarcinoma
title_short Comprehensive analysis of UPK3B as a marker for prognosis and immunity in pancreatic adenocarcinoma
title_sort comprehensive analysis of upk3b as a marker for prognosis and immunity in pancreatic adenocarcinoma
topic Pancreatic Cancer
Immunosuppression
MHC
Prognosis
Biomarker
url https://doi.org/10.1038/s41598-025-97213-x
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