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PMID: 33316775 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

B3GNT3 overexpression promotes tumor progression and inhibits infiltration of CD8+ T cells in pancreatic cancer.

Aging ·Vol. 13 ·No. 2 ·2020-00-09 ·Pages 2310-2329

Zhuang H, Zhou Z, Zhang Z, Chen X, Ma Z, Huang S, Gong Y, Zhang C, Hou B

Abstract

Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) has been associated with tumor progression in several solid tumors, and inhibits CD8+ T cell-mediated anti-tumor immunity in breast cancer. However, little is known about the potential functions of B3GNT3 in immunosuppression in pancreatic cancer (PC). This study on B3GNT3 aims to provide novel insights into the mechanisms of immune suppression or evasion in PC. To this end, the clinical significance and oncologic roles of B3GNT3 were investigated through bioinformatic analysis and in vitro studies. Potential associations between the expression of B3GNT3 and tumor immunity were mainly analyzed by single-sample gene set enrichment analysis (ssGSEA) and immunofluorescence in tissue microarray (TMA). B3GNT3 overexpression was observed in PC tissue and was associated with larger tumor sizes, higher histologic grades, and poorer overall survival (OS). B3GNT3 overexpression was associated with the mutation status and expression of driver genes, especially for KRAS and SMAD4. B3GNT3 knockdown inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of PC cells. B3GNT3 overexpression significantly correlated with decreased infiltration of tumor infiltrating lymphocytes (TILs), especially CD8+ T cells. Overall, our results indicate that B3GTN3 plays a novel role in tumor progression and immunosuppression, thus serving as a potential therapeutic target in PC.

Keywords
B3GNT3 CD8+ T cells TCGA pancreatic cancer tumor-infiltrating lymphocytes
MeSH Terms
Biomarkers, Tumor/genetics,metabolism CD8-Positive T-Lymphocytes/metabolism,pathology Cell Line, Tumor Cell Movement/genetics Cell Proliferation/genetics Computational Biology Databases, Genetic Disease Progression Epithelial-Mesenchymal Transition/genetics Female Gene Knockdown Techniques Humans Lymphocytes, Tumor-Infiltrating/metabolism,pathology Male Middle Aged N-Acetylglucosaminyltransferases/genetics,metabolism Neoplasm Invasiveness/genetics,pathology Pancreatic Neoplasms/genetics,metabolism,mortality,pathology Prognosis Proto-Oncogene Proteins p21(ras)/genetics,metabolism Smad4 Protein/genetics,metabolism Survival Rate
Chemicals
Biomarkers, Tumor KRAS protein, human SMAD4 protein, human Smad4 Protein B3GNT3 protein, human N-Acetylglucosaminyltransferases Proto-Oncogene Proteins p21(ras)
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zhuang Hongkai
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China. | Shantou University of Medical College, Shantou 515000, China.
Zhou Zixuan
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China.
Zhang Zedan
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China. | Shantou University of Medical College, Shantou 515000, China.
Chen Xinming
Department of Hepatobiliary Surgery, Shenshan Central Hospital, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Shanwei 516600, China.
Ma Zuyi
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China. | Shantou University of Medical College, Shantou 515000, China.
Huang Shanzhou
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China.
Gong Yuanfeng
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China.
Zhang Chuanzhao
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China.
Hou Baohua
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China. | The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510280, China.
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Article Info
Journal
Aging
Abbr.
Aging (Albany NY)
ISSN
1945-4589
DOI
10.18632/aging.202255
Published
2020-00-09
Epub
2020-00-09
Pages
2310-2329
Language
English
Region
United States
NLM ID
101508617
PMCID
PMC7880340
Subset
IM
External Links
PubMed source DOI: 10.18632/aging.202255 PMC Full Text View journal details
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