Frontiers in Cell and Developmental Biology (Jun 2022)

Integrated Analysis of Glutathione Metabolic Pathway in Pancreatic Cancer

  • Xingui Wu,
  • Xingui Wu,
  • Ruyuan Yu,
  • Ruyuan Yu,
  • Meisongzhu Yang,
  • Meisongzhu Yang,
  • Yameng Hu,
  • Yameng Hu,
  • Miaoling Tang,
  • Miaoling Tang,
  • Shuxia Zhang,
  • Shuxia Zhang,
  • Ainiwaerjiang Abudourousuli,
  • Ainiwaerjiang Abudourousuli,
  • Xincheng Li,
  • Xincheng Li,
  • Ziwen Li,
  • Ziwen Li,
  • Xinyi Liao,
  • Xinyi Liao,
  • Yingru Xu,
  • Yingru Xu,
  • Man Li,
  • Man Li,
  • Suwen Chen,
  • Suwen Chen,
  • Wanying Qian,
  • Wanying Qian,
  • Rongni Feng,
  • Rongni Feng,
  • Jun Li,
  • Jun Li,
  • Fenjie Li,
  • Fenjie Li

DOI
https://doi.org/10.3389/fcell.2022.896136
Journal volume & issue
Vol. 10

Abstract

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Metabolic enzyme-genes (MEs) play critical roles in various types of cancers. However, MEs have not been systematically and thoroughly studied in pancreatic cancer (PC). Global analysis of MEs in PC will help us to understand PC progressing and provide new insights into PC therapy. In this study, we systematically analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) (n = 180 + 4) and GSE15471 (n = 36 + 36) and discovered that metabolic pathways are disordered in PC. Co-expression network modules of MEs were constructed using weighted gene co-expression network analysis (WGCNA), which identified two key modules. Both modules revealed that the glutathione signaling pathway is disordered in PC and correlated with PC stages. Notably, glutathione peroxidase 2 (GPX2), an important gene involved in glutathione signaling pathway, is a hub gene of the key modules. Analysis of immune microenvironment components reveals that PC stage is associated with M2 macrophages, the marker gene of which is significantly correlated with GPX2. The results indicated that GPX2 is associated with PC progression, providing new insights for future targeted therapy.

Keywords