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

IF 5.3
Fengchen Jiang, Shuiping Zhou, Chuanlong Xia, Jiale Lu, Bin Wang, Xiaowei Wang, Jiandong Shen, Wei Ding, Mengjie Yin, Feng Dai, Shouzhong Fu
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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.

Abstract Image

GLYAT 的下调与肝细胞癌的肿瘤进展和预后不良有关。
众所周知,甘氨酸 N-酰基转移酶(GLYAT)会影响甘氨酸的代谢,它与各种恶性肿瘤的进展有关。然而,它在肝细胞癌(HCC)中的临床意义仍有待探索。与正常肝组织相比,GLYAT 在 HCC 组织中的表达水平明显降低。同样,GLYAT在Huh 7、HepG2、PLC和SK-HEP1中的表达水平也低于LO2。接收者操作特征曲线分析表明,GLYAT 对 HCC 具有良好的诊断性能。Kaplan-Meier分析表明,GLYAT表达的降低与HCC的恶化相关。GLYAT的低表达与性别和组织学分级明显相关。多变量 Cox 回归分析发现,GLYAT 低表达和 T 分期是独立的预后因素。基于GLYAT mRNA表达和T分期的提名图与1年、2年、3年和5年的实际生存率显示出良好的一致性。此外,在Huh 7细胞系中GLYAT下调会增强细胞的增殖、侵袭和迁移能力,而在HepG2细胞系中GLYAT过表达则会抑制这些能力。GLYAT 低表达的 HCC 患者易发生免疫逃逸,对免疫疗法的反应较差。这项研究表明,GLYAT有望成为HCC的预后生物标志物和潜在治疗靶点。
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来源期刊
CiteScore
11.50
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0.00%
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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