B4GALNT1 通过调控泛癌分析中的上皮-间充质转化促进肝癌发生。

B4GALNT1 promotes carcinogenesis by regulating epithelial-mesenchymal transition in hepatocellular carcinoma based on pan-cancer analysis.

机构信息

Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College & China Academy of Medical Science, Beijing, China.

Department of Clinical Laboratory, Second People's Hospital of Lanzhou, Lanzhou, Gansu, China.

出版信息

J Gene Med. 2023 Nov;25(11):e3552. doi: 10.1002/jgm.3552. Epub 2023 Jun 20.

DOI:10.1002/jgm.3552

PMID:37337736

Abstract

BACKGROUND

β-1,4-N-Acetyl galactosaminyltransferase1 (B4GALNT1) has been reported to play important roles in tumor progression and metastasis. Herein, we investigate the oncogenic roles of B4GALNT1 for hepatocellular carcinoma (HCC) based on immune microenvironment.

METHODS

The Cancer Genome Atlas database and Genotype-Tissue Expression, cBioportal, ImmuCellAI, TIMER2 and other databases were searched to analyze the expression and clinical applications of B4GALNT1 in liver cancer patients. Kaplan-Meier survival analysis, Cox regression analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis were utilized. Moreover, western blot assay, immune histochemistry staining, Cell Counting Kit-8 (CCK-8) assay, invasion and migration assay were performed to evaluate the function of B4GALNT1 in HCC.

RESULTS

B4GALNT1 is overexpressed in 14 tumors, and the mRNA expression levels of B4GALNT1 were remarkably elevated in most tumor types, including HCC. In addition, B4GALNT1 expression was an independent prognostic factor, and a low expression of B4GALNT1 showed a better overall survival and disease-specific recurrence-free survival in patients with HCC. Gene set variation analysis indicated that B4GALNT1 presented a positive correlation with the epithelial-mesenchymal transition (EMT) pathway in HCC. B4GALNT1 expression was closely associated with immune activation genes in the HCC microenvironment. Moreover, B4GALNT1 expression was higher in HCC tissue than that in surrounding tissues. B4GALNT1 promoted the expression of apoptosis-related or EMT-related proteins and then decreased the expression of Bcl-2 and Bcl-xl in HCC cells, suggesting that B4GALNT1 knockdown significantly inhibited the proliferation and invasion of HCC cells.

CONCLUSIONS

B4GALNT1 may promote HCC development through regulating the EMT pathway, which suggests that B4GALNT1 may serve as a promising predictive biomarker and a potential therapeutic target for HCC.

摘要

背景

β-1,4-N-乙酰半乳糖胺基转移酶 1（B4GALNT1）已被报道在肿瘤进展和转移中发挥重要作用。在此，我们基于免疫微环境研究 B4GALNT1 对肝细胞癌（HCC）的致癌作用。

方法

搜索癌症基因组图谱数据库和基因-组织表达、cBioportal、ImmuCellAI、TIMER2 和其他数据库，分析 B4GALNT1 在肝癌患者中的表达和临床应用。进行 Kaplan-Meier 生存分析、Cox 回归分析、京都基因与基因组百科全书和基因本体论富集分析。此外，进行 Western blot 检测、免疫组织化学染色、细胞计数试剂盒-8（CCK-8）检测、侵袭和迁移实验，以评估 B4GALNT1 在 HCC 中的功能。

结果

B4GALNT1 在 14 种肿瘤中过度表达，并且 B4GALNT1 的 mRNA 表达水平在大多数肿瘤类型中显著升高，包括 HCC。此外，B4GALNT1 表达是一个独立的预后因素，HCC 患者中 B4GALNT1 低表达的总生存率和疾病特异性无复发生存率较好。基因集变异分析表明，B4GALNT1 在 HCC 中与上皮-间充质转化（EMT）途径呈正相关。B4GALNT1 的表达与 HCC 微环境中的免疫激活基因密切相关。此外，B4GALNT1 在 HCC 组织中的表达高于周围组织。B4GALNT1 促进凋亡相关或 EMT 相关蛋白的表达，然后降低 HCC 细胞中 Bcl-2 和 Bcl-xl 的表达，表明 B4GALNT1 敲低显著抑制 HCC 细胞的增殖和侵袭。