The pan-cancer landscape of glutamate and glutamine metabolism: A comprehensive bioinformatic analysis across 32 solid cancer types

Wenhua Xue; Kai Wu; Xiaona Guo; Chengxin Chen; Tao Huang; Lifeng Li; Bin Liu; Hao Chang; Jie Zhao

doi:10.1016/j.bbadis.2023.166982

The pan-cancer landscape of glutamate and glutamine metabolism: A comprehensive bioinformatic analysis across 32 solid cancer types

Biochim Biophys Acta Mol Basis Dis. 2024 Feb;1870(2):166982. doi: 10.1016/j.bbadis.2023.166982. Epub 2023 Dec 6.

Authors

Wenhua Xue¹, Kai Wu², Xiaona Guo³, Chengxin Chen⁴, Tao Huang³, Lifeng Li⁵, Bin Liu⁶, Hao Chang⁷, Jie Zhao⁸

Affiliations

¹ Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Medical School, Huanghe Science and Technology University, Zhengzhou 450052, China. Electronic address: fccxuewh@zzu.edu.cn.
² Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
³ Medical School, Huanghe Science and Technology University, Zhengzhou 450052, China.
⁴ Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Internet Medical and System Applications of National Engineering Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
⁵ Internet Medical and System Applications of National Engineering Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
⁶ Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, China.
⁷ Department of Cancer Research, Hanyu Biomed Center Beijing, Beijing 102488, China. Electronic address: changhao@hanyu-biomed.org.
⁸ Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Internet Medical and System Applications of National Engineering Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: zhaojie@zzu.edu.cn.

PMID: 38065270
DOI: 10.1016/j.bbadis.2023.166982

Abstract

Glutamine metabolism is a hallmark of cancer metabolism, which matters in the progression of the tumor. This synthetic study conducted a large-scale systematic analysis at the pan-cancer level on the glutamate and glutamine metabolism (GGM) across 32 solid tumors from the TCGA database. The glutamine metabolism activity was quantified through a scoring system. This study revealed that the GGM score in tumor tissues was up-regulated in 13 cancer types (BCLA, BRCA, COAD, KICH, KIRP, LUAD, LUSC, PAAD, PRAD, READ, STAD, THYM, UCEC) and down-regulated in 4 cancer types (CHOL, GBM, LIHC, THCA), exhibiting tissue specificity. The mRNA expression levels of glutamine metabolism-related genes were relatively high, and GLUL exhibited the highest expression level. The expression levels were up-regulated with copy number amplification. ALDH18A1, PYCR1, and PYCR2 show a significant upregulation in protein levels in cancer tissues compared to normal tissues, making them potential pan-cancer therapeutic targets. For the TME related to glutamine metabolism, the GGM score exhibited significant immune and stromal environment inhibitory effects in all involved tumors. Up-regulated GGM score indicated the widespread promotion of drug resistance at the pan-cancer level. GGM score and glutamine metabolism-related genes signature tended to be risk factors for the overall survival of cancer patients.

Keywords: Drug sensitivity; Genetic alternations; Glutamate and glutamine metabolism; Molecular subtypes; Prognosis; Tumor microenvironment.

MeSH terms

Computational Biology
Glutamic Acid*
Glutamine
Humans
Neoplasms* / genetics
Up-Regulation

Substances

Glutamic Acid
Glutamine