High SLC2A1 expression associated with suppressing CD8 T cells and B cells promoted cancer survival in gastric cancer

PLoS One. 2021 Mar 18;16(3):e0245075. doi: 10.1371/journal.pone.0245075. eCollection 2021.

Abstract

High expression of glucose transporter family members, which augment glucose uptake and glycolytic flux, has been shown to play a pivotal role in the proliferation and survival of tumor cells, contributing to the energy supply, biosynthesis and homeostasis of cancer cells. Among the many members, solute carrier family 2 member 1 (SLC2A1) encodes a glucose transporter, GLUT1, that is critical in the metabolism of glucose, which is an energy source for cell growth that contributes to cancer progression and development. The aim of this study was to analyze the survival and genetic changes/immune profiles in patients with gastric cancer with high SLC2A1 expression and to provide treatment for improving prognosis. This study investigated the clinicopathologic parameters, the proportion of immune cells and gene sets affecting SLC2A1 expression in 279 and 415 patients with gastric cancer from the Eulji Hospital cohort and The Cancer Genome Atlas, respectively. We assessed the response to conventional chemotherapy drugs, including fluorouracil, a compound of fluoropyrimidine S-1, oxaliplatin, and all-trans-retinoic acid (ATRA), in gastric cancer cell lines with high SLC2A1 expression. High SLC2A1 expression was associated with poor prognosis, cancer cell proliferation, decreased immune cells, including CD8 T cells and B cells, and a low prognostic nutrition index, representing body nutrition-related status. In pathway network analysis, SLC2A1 was indirectly linked to the retinoic signaling pathway and negatively regulated immune cells/receptors. In the drug response analysis, the drug ATRA inhibited gastric cancer cell lines with high SLC2A1 expression. Treatment involving the use of SLC2A1 could contribute to better clinical management/research for patients with gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Copy Number Variations
  • Disease-Free Survival
  • Down-Regulation / drug effects
  • Female
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Survival Rate
  • Tretinoin / pharmacology
  • Tretinoin / therapeutic use

Substances

  • Antineoplastic Agents
  • Glucose Transporter Type 1
  • SLC2A1 protein, human
  • Tretinoin

Grants and funding

YES This study was supported by Daewon Pharmaceutical Co., Ltd. in 2018. (To Byoung Kwan Son). The funding organization did not play any role in our study and provided only financial support. We have reviewed the author roles in the Author Contribution section and confirm the previous statements are correctly stated.