HBV Infection-Related PDZK1 Plays an Oncogenic Role by Regulating the PI3K-Akt Pathway and Fatty Acid Metabolism and Enhances Immunosuppression

Background and Aim. Chronic hepatitis B virus (HBV) infection is the leading global cause of hepatocellular carcinoma (HCC). Few studies have been conducted concerning the HBV infection-related genes and their function. Methods. We compared differentially expressed genes (DGEs) in HBV-positive and -...

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Main Authors: Xin Chen, Xiaodong Wang, Feng Zhu, Chao Qian, Fanggui Xu, Xin Huang, Wenjie Zhang, Beicheng Sun
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/8785567
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author Xin Chen
Xiaodong Wang
Feng Zhu
Chao Qian
Fanggui Xu
Xin Huang
Wenjie Zhang
Beicheng Sun
author_facet Xin Chen
Xiaodong Wang
Feng Zhu
Chao Qian
Fanggui Xu
Xin Huang
Wenjie Zhang
Beicheng Sun
author_sort Xin Chen
collection DOAJ
description Background and Aim. Chronic hepatitis B virus (HBV) infection is the leading global cause of hepatocellular carcinoma (HCC). Few studies have been conducted concerning the HBV infection-related genes and their function. Methods. We compared differentially expressed genes (DGEs) in HBV-positive and -negative tumor samples and conducted a Spearman correlation study between the DGEs and HBV titers within The Cancer Genome Atlas (TCGA). Moreover, we validated the results of our in-house samples. Results. In this study, we discovered a series of genes that correlated statistically with HBV infection based on the TCGA database. These genes were related to increased inflammation and some oncogenic signaling pathways via Gene Set Enrichment Analysis (GSEA). PDZK1 is an ideal gene, which mostly relates positively to HBV infection; moreover, it is overexpressed in human HCC, especially in those HBV-infected HCCs. After analyzing the TCGA data and performing a verification study using our own samples, PDZK1 expression was investigated to be significantly associated with PI3K-Akt signaling and fatty acid metabolism. Further, single-sample GSEA analysis of tumor immune cell infiltration gene sets revealed that high PDZK1expression in HCC tissues was significantly associated with increased tumor-associated macrophages (TAMs) and regulatory T cells(Tregs). Conclusions. PDZK1 is an HBV infection-related gene, which plays oncogenic roles, possibly due to enhancing PI3K-Akt, fatty acid usage in tumor cells and TAMs, and Treg-induced immunosuppression.
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spelling doaj-art-d15094c901ad4358a5a3beb8666e98ee2025-08-20T02:19:57ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/8785567HBV Infection-Related PDZK1 Plays an Oncogenic Role by Regulating the PI3K-Akt Pathway and Fatty Acid Metabolism and Enhances ImmunosuppressionXin Chen0Xiaodong Wang1Feng Zhu2Chao Qian3Fanggui Xu4Xin Huang5Wenjie Zhang6Beicheng Sun7Department of Hepatobilliary Surgery of Drum Tower Clinical Medical CollegeDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of General SurgeryDepartment of Hepatobilliary Surgery of Drum Tower Clinical Medical CollegeDepartment of Hepatobilliary Surgery of Drum Tower Clinical Medical CollegeBackground and Aim. Chronic hepatitis B virus (HBV) infection is the leading global cause of hepatocellular carcinoma (HCC). Few studies have been conducted concerning the HBV infection-related genes and their function. Methods. We compared differentially expressed genes (DGEs) in HBV-positive and -negative tumor samples and conducted a Spearman correlation study between the DGEs and HBV titers within The Cancer Genome Atlas (TCGA). Moreover, we validated the results of our in-house samples. Results. In this study, we discovered a series of genes that correlated statistically with HBV infection based on the TCGA database. These genes were related to increased inflammation and some oncogenic signaling pathways via Gene Set Enrichment Analysis (GSEA). PDZK1 is an ideal gene, which mostly relates positively to HBV infection; moreover, it is overexpressed in human HCC, especially in those HBV-infected HCCs. After analyzing the TCGA data and performing a verification study using our own samples, PDZK1 expression was investigated to be significantly associated with PI3K-Akt signaling and fatty acid metabolism. Further, single-sample GSEA analysis of tumor immune cell infiltration gene sets revealed that high PDZK1expression in HCC tissues was significantly associated with increased tumor-associated macrophages (TAMs) and regulatory T cells(Tregs). Conclusions. PDZK1 is an HBV infection-related gene, which plays oncogenic roles, possibly due to enhancing PI3K-Akt, fatty acid usage in tumor cells and TAMs, and Treg-induced immunosuppression.http://dx.doi.org/10.1155/2022/8785567
spellingShingle Xin Chen
Xiaodong Wang
Feng Zhu
Chao Qian
Fanggui Xu
Xin Huang
Wenjie Zhang
Beicheng Sun
HBV Infection-Related PDZK1 Plays an Oncogenic Role by Regulating the PI3K-Akt Pathway and Fatty Acid Metabolism and Enhances Immunosuppression
Journal of Immunology Research
title HBV Infection-Related PDZK1 Plays an Oncogenic Role by Regulating the PI3K-Akt Pathway and Fatty Acid Metabolism and Enhances Immunosuppression
title_full HBV Infection-Related PDZK1 Plays an Oncogenic Role by Regulating the PI3K-Akt Pathway and Fatty Acid Metabolism and Enhances Immunosuppression
title_fullStr HBV Infection-Related PDZK1 Plays an Oncogenic Role by Regulating the PI3K-Akt Pathway and Fatty Acid Metabolism and Enhances Immunosuppression
title_full_unstemmed HBV Infection-Related PDZK1 Plays an Oncogenic Role by Regulating the PI3K-Akt Pathway and Fatty Acid Metabolism and Enhances Immunosuppression
title_short HBV Infection-Related PDZK1 Plays an Oncogenic Role by Regulating the PI3K-Akt Pathway and Fatty Acid Metabolism and Enhances Immunosuppression
title_sort hbv infection related pdzk1 plays an oncogenic role by regulating the pi3k akt pathway and fatty acid metabolism and enhances immunosuppression
url http://dx.doi.org/10.1155/2022/8785567
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