Research Paper Volume 13, Issue 2 pp 2310—2329
B3GNT3 overexpression promotes tumor progression and inhibits infiltration of CD8+ T cells in pancreatic cancer
- 1 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
- 2 Shantou University of Medical College, Shantou 515000, China
- 3 Department of Hepatobiliary Surgery, Shenshan Central Hospital, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Shanwei 516600, China
- 4 The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510280, China
Received: February 28, 2020 Accepted: November 3, 2020 Published: December 9, 2020
https://doi.org/10.18632/aging.202255How to Cite
Copyright: © 2021 Zhuang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
PC: Pancreatic cancer; B3GNT3: Beta-1,3-N-acetylglucosaminyltransferase 3; TCGA: The Cancer Genome Atlas; OS: overall survival; KM: Kaplan-Meier; GSEA: Gene Set Enrichment Analysis; ssGSEA: single sample Gene Set Enrichment Analysis; AJCC: the American Joint Committee on Cancer; KEGG: Kyoto Encyclopedia of Gens and Genomes; HPA: The human protein atlas; TGF-β: transforming growth factor β; MET: epithelia-mesenchymal transition; TILs: tumor-infiltrating lymphocytes; TME: tumor microenvironment; Th1 cells: Type-1 T helper cells; Th2/Th1: Type-2 T helper cells/ Type-1 T helper cells; TMA: tissue microarray; shRNA: small hairpin RNA; OD: optical density; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis; qRT-PCR: Quantitative real-time reverse transcription polymerase chain reaction; DMSO: Dimethyl sulfoxide.