A pancancer analysis reveals the oncogenic role of glutaminase 1 (GLS1) in tumor metabolism and immune evasion: a bioinformatics analysis

Our plain-English summary of A pancancer analysis reveals the oncogenic role of glutaminase 1 (GLS1) in tumor metabolism and immune evasion: a bioinformatics analysis, by J. Liu, S. Hong, K. Gu (Discover Oncology, 2025).

The study

• Authors: J. Liu, S. Hong, K. Gu
• Journal: Discover Oncology
• Published: 2025;16(1):2156
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Metabolic reprogramming is a significant factor that regulates the function and differentiation of immune cells, thereby influencing the progress of the immune response. The intricate interplay between glutamine metabolism and the immune microenvironment (TME) plays crucial roles in the pathogenesis of cancer. The initiation of glutamine metabolism is facilitated by the enzyme GLS1; however, its oncogenic role remains unclear.

Methods: In this pancancer analysis, we aimed to investigate the potential oncogenic mechanism of GLS1 across various tumor types in The Cancer Genome Atlas (TCGA) dataset.

Results: Our results revealed variable expression levels of GLS1 across different cancer types. Notably, higher expression levels of GLS1 were associated with worse prognosis in patients with kidney renal papillary cell carcinoma (KIRP, HR = 1.01; p < 0.01), liver hepatocellular carcinoma (LIHC, HR = 1.02; p < 0.01), and mesothelioma (MESO, HR = 1.01; p < 0.01). Additionally, we observed distinct associations between GLS1 expression levels and tumor methylation levels, tumor mutation burden (TMB), microsatellite instability (MSI), immune cell infiltration (IFL), and immune scores in several tumor types. We also detected the enrichment of GLS1 in key pathways, such as the mTOR, JAK, and KRAS pathways. Furthermore, we observed associations between GLS1 expression levels and a wide range of immune checkpoint genes, including both immunoinhibitors and immunostimulators, in most tumors.

Conclusions: Our study provides initial insights into the oncogenic roles of GLS1 across different tumors. These findings suggest that GLS1 can serve as a potential biomarker for determining prognosis and designing therapeutic strategies for various tumor types.

© 2025. The Author(s).

In plain English

This was a bioinformatics study. The authors analyzed publicly available databases, mainly The Cancer Genome Atlas (TCGA), to examine a gene called GLS1, which is involved in glutamine metabolism, across 33 tumor types. Mesothelioma was one of these tumor types. The article did not study asbestos or any other exposure, and it did not say how many mesothelioma patients were included. GLS1 expression was higher than in normal tissue in 11 tumor types and lower in the rest. Genetic alterations in GLS1 were rare (0.9%). Higher GLS1 expression was associated with poorer overall survival in mesothelioma (hazard ratio 1.01, p less than 0.01), and also in kidney renal papillary cell carcinoma and liver hepatocellular carcinoma. GLS1 expression was also linked to disease-specific survival in mesothelioma (hazard ratio 1.01, p = 0.03). In mesothelioma, GLS1 expression was negatively correlated with an immune score (r = -0.26). Across most cancers, GLS1 expression was correlated with immune checkpoint genes. The authors concluded that the results may help in understanding the oncogenic roles of GLS1. They stated that their findings need validation in animal and clinical studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatics (pan-cancer) analysis of publicly available gene and protein expression databases
• Who was studied: Tumor samples from 33 tumor types in The Cancer Genome Atlas (TCGA), including mesothelioma (MESO). Comparisons used normal tissue from the GTEx project (54 tissue sites, over 1,000 individuals) and 21 types of cancer cell lines. The number of patients per tumor type, including mesothelioma, was not stated in the text.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The variable examined was GLS1 gene and protein expression in tumor and normal tissues.
• Main results:
  • Across tumor types, 11 tumors showed greater GLS1 expression than normal tissues; the remaining tumors showed lower expression.
  • Genetic alterations in GLS1 across tumor samples were very rare (0.9%).
  • Higher GLS1 expression was associated with poorer overall survival in patients with kidney renal papillary cell carcinoma (HR = 1.01; p < 0.01), liver hepatocellular carcinoma (HR = 1.02; p < 0.01) and mesothelioma (HR = 1.01; p < 0.01). Confidence intervals are not printed in the text.
  • In disease-specific survival analysis, GLS1 expression was correlated with survival in mesothelioma patients (HR = 1.01; p = 0.03).
  • In mesothelioma patients, GLS1 expression was negatively correlated with the ImmuneScore (r = -0.26, p = 0.016).
  • GLS1 expression was positively correlated with DNA methylation enzymes (DNMTs) in 15 of 33 tumor types. Mesothelioma was listed among the exceptions.
  • GLS1 expression was associated with immune checkpoint gene expression in most cancer types, except cholangiocarcinoma and uterine carcinosarcoma.
  • Pathway analysis suggested that higher GLS1 expression may be involved in the mTOR signaling pathway and leukocyte transendothelial migration.
• The authors' conclusion: The authors concluded that their observations showed GLS1 affects the energy metabolism of cells as well as the epigenetics and response of tumors, and that the results may facilitate understanding of the oncogenic roles of GLS1.
• Limitations the authors state:
  • The suggestion that GLS1 may be a biomarker comes from database analyses and requires validation through animal and clinical studies.
  • Glutamine metabolism is also influenced by other enzymes (SLC1A5 and SLC7A5), which were not analyzed.
  • No survival difference between mutated and wild-type GLS1 could be detected because GLS1 mutations were rare in the TCGA data.

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Carcinoma, Mesothelioma, Microsatellite Instability (MSI-H), Biomarker.

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