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. 2024 Nov;28(21):e70197.
doi: 10.1111/jcmm.70197.

Downregulation of GLYAT correlates with tumour progression and poor prognosis in hepatocellular carcinoma

Fengchen Jiang  1   2 , Shuiping Zhou  1   2   3 , Chuanlong Xia  1   3 , Jiale Lu  1   3 , Bin Wang  1 , Xiaowei Wang  1 , Jiandong Shen  1 , Wei Ding  1 , Mengjie Yin  1 , Feng Dai  1 , Shouzhong Fu  1
Affiliations

Downregulation of GLYAT correlates with tumour progression and poor prognosis in hepatocellular carcinoma

Fengchen Jiang et al. J Cell Mol Med. 2024 Nov.

Abstract

Glycine N-acyltransferase (GLYAT), known to influence glycine metabolism, has been implicated in the progression of various malignant tumours. However, its clinical relevance in hepatocellular carcinoma (HCC) remains unexplored. Here, GLYAT expression levels in HCC tissues were significantly reduced compared to normal liver tissues. Similarly, GLYAT expression levels in Huh 7, HepG2, PLC and SK-HEP1 were lower than those in LO2. Receiver operating characteristic curve analysis demonstrated that GLYAT exhibited good diagnostic performance for HCC. Kaplan-Meier analyses suggested that decreased GLYAT expression was correlated with poorer progress in HCC. Low GLYAT expression was significantly associated with gender and histologic grade. Multivariate Cox regression analysis identified low GLYAT expression and T stage as independent prognostic factors. Nomograms based on GLYAT mRNA expression and T stage showed good concordance with actual survival rates at 1, 2, 3 and 5 years. Moreover, GLYAT downregulation in the Huh 7 cell line enhanced cell proliferation, invasion and migration abilities, while GLYAT overexpression in the HepG2 cell line inhibited these abilities. HCC patients with low GLYAT expression exhibited a predisposition to immune escape and poor response to immunotherapy. This research revealed that GLYAT holds promise as both a prognostic biomarker and a potential therapeutic target in HCC.

Keywords: GLYAT; hepatocellular carcinoma; immunotherapy; prognosis; tumour progression.

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Conflict of interest statement

The authors confirm that there are no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Expression of GLYAT and its diagnostic value in HCC patients. (A, B) The mRNA expression of GLYAT in HCC and paired normal tissues was analysed based on the TCGA and GEO databases. (C–G) RT‐qPCR, Western blotting and IHC were used to analyse the GLYAT expression in fresh HCC tissues and corresponding normal tissues. T, tumour; N, normal. (H) Diagnostic value of GLYAT downregulation for HCC using ROC curve. ***p < 0.001. Scale bars for F are 200 and 50 μm.
FIGURE 2
FIGURE 2
The deficiency of GLYAT predicts poor prognosis in HCC. (A–D) Kaplan–Meier analysis of OS, DFI, DSS and PFI according to GLYAT expression in TCGA database. (E, F) Kaplan–Meier analysis of OS in GEO and ICGC databases.
FIGURE 3
FIGURE 3
Validation of the prognostic value of GLYAT in HCC. (A) Nomogram predicting the probability of HCC patients' mortality based on three prognostic signatures. (B–E) Calibration curves of the nomogram.
FIGURE 4
FIGURE 4
GLYAT suppresses HCC cells proliferation and metastasis in vitro. (A, B) The migration and invasion abilities of Huh 7‐ctrl, Huh 7‐sh and HepG2‐ctrl, HepG2‐oe detected by wound healing assays. (C, D) The proliferation abilities of Huh 7‐ctrl, Huh 7‐sh and HepG2‐ctrl, HepG2‐oe detected by colony formation assays. (E–H) The migration and invasion abilities of Huh 7‐ctrl, Huh 7‐sh and HepG2‐ctrl, HepG2‐oe detected by invasion and migration assays. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. Scale bars for A, E, G are 200 μm.
FIGURE 5
FIGURE 5
The landscape of tumour immune microenvironment. (A) StromalScore, ImmuneScore and ESTIMATEScore between high‐ and low‐GLYAT group in TCGA. (B) Correlation between GLYAT expression and immune cells in TCGA. (C) Relative cell abundance immune cells by CIBERSORT between two groups in TCGA. *p < 0.05; **p < 0.01; ***p < 0.001.
FIGURE 6
FIGURE 6
The estimation of Immunotherapy response. (A–D) The association between high‐ and low‐GLYAT group and immunophenoscore (IPS). (E) The correlation between the expression of immune checkpoint genes and GLYAT expression.
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