The expression and prognostic value of GLYATL1 and its potential role in hepatocellular carcinoma

Renguo Guan; Weifeng Hong; Jianfeng Huang; Tianyi Peng; Zhen Zhao; Ye Lin; Min Yu; Zhixiang Jian

doi:10.21037/jgo-20-186

The expression and prognostic value of GLYATL1 and its potential role in hepatocellular carcinoma

J Gastrointest Oncol. 2020 Dec;11(6):1305-1321. doi: 10.21037/jgo-20-186.

Authors

Renguo Guan^{1

2}, Weifeng Hong³, Jianfeng Huang², Tianyi Peng², Zhen Zhao², Ye Lin², Min Yu², Zhixiang Jian^{1

2}

Affiliations

¹ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
² Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
³ Department of Medical Imaging, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.

Abstract

Background: Glycine-N-acyltransferase-like 1 (GLYATL1), which is involved in the detoxification of endogenous and exogenous acyl-CoA, promotes glutamine metabolism in xenobiotic metabolism. Recent evidence suggests an association between GLYATL1 and tumors. However, there are few comprehensive analyses of GLYATL1 in cancers. We evaluated the expression and prognostic value of GLYATL1 and explored the mechanism underlying the association between GLYATL1 and cancers.

Methods: GLYATL1 mRNA expression across cancers was investigated in the Oncomine database and confirmed in the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Next, its prognostic value in different cancers was revealed by PrognoScan and Kaplan-Meier plotter. According to clinicopathologic features, we conducted a subgroup analysis of the prognosis of GLYATL1 in a cohort of hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas (TCGA) and the GSE116174 dataset. We further investigated the GLYATL1 promoter methylation profile in HCC. Next, a protein-protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Finally, we utilized gene set enrichment analysis (GSEA) to identify significantly enriched pathways and confirmed their associations using the Tumor Immune Estimation Resource (TIMER) and GEPIA databases.

Results: GLYATL1 is downregulated in many cancers and indicates a poor prognosis. Specifically, low GLYATL1 expression was associated with short overall survival (OS) in HCC patients. Interestingly, GLYATL1 expression was associated with poor OS in stage I-II HCC patients and was revealed as an independent prognostic factor. The promoter methylation level of GLYATL1 in HCC tissue was significantly higher than that in normal liver tissue. The PPI network suggested that GLYATL1 is co-expressed with ten genes, including CNGA3 and GNB5. GSEA revealed that GLYATL1 is predominantly negatively enriched in xenobiotic metabolism, and the gene association analysis in TIMER and GEPIA showed a significantly negative association between the expression of GLYATL1 and the expression of most genes involved in mitochondrial glutamine metabolism, including SLC1A5 and SLC1A11.

Conclusions: Our study is the first to shed light on the expression and prognostic value of GLYATL1 in cancers and provide a potential regulatory mechanism underlying HCC development.

Keywords: GLYATL1; biomarker; glutamine; hepatocellular carcinoma (HCC); prognosis.