Bie Lihan, Chen Guangquan, Lei Xin, Xiao Feng, Xu Zheng, Xiang Zhouhong, Lu Zhicheng, Jiang Xiudi
Department of Laboratory Medicine, The Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai Key Laboratory of Maternal-Fetal Medicine, Department of Fetal Medicine and Prenatal Diagnosis Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
J Clin Lab Anal. 2025 Feb;39(4):e25155. doi: 10.1002/jcla.25155. Epub 2025 Jan 19.
Hepatocellular carcinoma (HCC) is a ubiquitous malignancy linked to significant mortality. The abnormal expression of β-1,4-N-acetyl-galactosaminyltransferase 1 (B4GALNT1) seemed to be implicated in tumorigenesis. Nonetheless, this enzyme's roles in HCC are unclear.
By analyzing the TCGA_LIHC, GSE77509, and GSE135631 datasets, the levels of B4GALNT1 expression in HCC and surrounding non-cancerous tissues were compared. The prognostic implications of B4GALNT1 were assessed using the Cox regression analysis (CRA). The relationship of B4GALNT1 mutations with CpG island methylation levels and prognosis was examined by analyzing the cBioPortal and MethSurv databases. We sifted the evidence of B4GALNT1 expression correlating with 28 immune cell types' infiltration by harnessing the "GSVA" R package. To delve into the influences of genes associated with B4GALNT1 on HCC, we implemented gene set enrichment analysis (GSEA). We constructed a lentiviral vector expressing B4GALNT1 and knocked down B4GALNT1 in HepG2 cells. The resulting effects on HCC cell proliferation and apoptosis were analyzed via cell proliferation assays and flow cytometry.
HCC tissues presented significant B4GALNT1 overexpression relative to surrounding non-cancerous tissues, marking it as a standalone risk factor for HCC progression. Methylation levels of two CpG islands were high, suggesting poor prognosis. It was detectable that B4GALNT1 expression interrelated with the infiltration extent of natural killer T cells in HCC tissues. B4GALNT1-fueled cell proliferation and enhanced resistance to apoptosis in HCC cells.
B4GALNT1 is a strong regulator of HCC progression and holds promise as a marker for prognosis and a hallmark for therapy in HCC.
肝细胞癌（HCC）是一种普遍存在且死亡率很高的恶性肿瘤。β-1,4-N-乙酰半乳糖胺基转移酶1（B4GALNT1）的异常表达似乎与肿瘤发生有关。然而，这种酶在HCC中的作用尚不清楚。
通过分析TCGA_LIHC、GSE77509和GSE135631数据集，比较了HCC组织和周围非癌组织中B4GALNT1的表达水平。使用Cox回归分析（CRA）评估B4GALNT1的预后意义。通过分析cBioPortal和MethSurv数据库，研究了B4GALNT1突变与CpG岛甲基化水平及预后的关系。我们利用“GSVA”R包筛选了B4GALNT1表达与28种免疫细胞类型浸润相关的证据。为了深入研究与B4GALNT1相关的基因对HCC的影响，我们进行了基因集富集分析（GSEA）。我们构建了表达B4GALNT1的慢病毒载体，并在HepG2细胞中敲低B4GALNT1。通过细胞增殖试验和流式细胞术分析了对HCC细胞增殖和凋亡的影响。
相对于周围非癌组织，HCC组织中B4GALNT1显著过表达，这使其成为HCC进展的独立危险因素。两个CpG岛的甲基化水平较高，提示预后不良。可检测到B4GALNT1表达与HCC组织中自然杀伤T细胞的浸润程度相关。B4GALNT1促进HCC细胞增殖并增强其对凋亡的抵抗能力。
B4GALNT1是HCC进展的强调节因子，有望作为HCC预后的标志物和治疗的靶点。
