国际口腔医学杂志

国际口腔医学杂志 ›› 2026, Vol. 53 ›› Issue (2): 189-196.doi: 10.7518/gjkq.2026211

• 论著 • 上一篇    下一篇

β-1,4-N-乙酰半乳糖胺基转移酶4在头颈部鳞状细胞癌中的表达规律及功能初探

刘明(),周妍亭,李敬()   

  1. 口腔疾病防治全国重点实验室 国家口腔医学中心 口腔疾病国家临床医学研究中心 四川大学华西口腔医院口腔癌发生与治疗研究单位 成都 610041
  • 收稿日期:2024-09-29 修回日期:2025-09-27 出版日期:2026-03-01 发布日期:2026-02-13
  • 通讯作者: 李敬
  • 作者简介:刘明，硕士，Email：liu01and0304@163.com
  • 基金资助:
    国家自然科学基金(82273320);国家自然科学基金(82472686)

Preliminary study on the expression pattern and function of β-1,4-N-acetyl-galactosaminyltransferase 4 in head and neck squamous cell carcinoma

Ming Liu(),Yanting Zhou,Jing Li()   

  1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2024-09-29 Revised:2025-09-27 Online:2026-03-01 Published:2026-02-13
  • Contact: Jing Li
  • Supported by:
    National Natural Science Foundation of China(82273320)

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摘要：

目的 通过生物信息学技术分析筛选转移和非转移型头颈鳞状细胞癌（HNSCC）组织中基因的表达规律，进一步筛选转移相关关键分子。 方法 从癌症基因组图谱数据集中选取了具有明确信息的19例HNSCC转移型和48例HNSCC非转移型患者的相关数据，通过生物信息学技术分析筛选在转移、非转移型HNSCC中上调和下调的差异表达基因，并对其进行聚类分析、京都基因与基因组百科全书分析和基因本体论分析。其中β-1,4-N-乙酰半乳糖胺基转移酶4（B4GALNT4）因其“调整后的P值”最小从而被选为关键基因，并通过逆转录及定量反转录聚合酶链式反应、蛋白免疫印迹实验对其进行细胞水平验证。 结果 与非转移型HNSCC组织相比，转移型中有76个基因显著下调，99个基因显著上调，其中B4GALNT4基因表达上调最显著。细胞水平检测发现，与转移能力弱的UM-2细胞相比，转移能力强的UM-1细胞中B4GALNT4的mRNA水平和蛋白表达水平均显著增加（P<0.05）；与UM-2细胞相比，UM-1细胞中蛋白O-糖基化的水平也显著增加（P<0.05）。 结论 B4GALNT4在转移型HNSCC组织和细胞中均表达上调，其表达与蛋白质糖基化的水平呈正相关关系，B4GALNT4有望成为一个肿瘤转移防治新靶点。

关键词: 头颈部鳞状细胞癌, 转移, β-1,4-N-乙酰半乳糖胺基转移酶 4, 糖基化

Abstract:

Objective　To screen differentially expressed genes in metastatic and non-metastatic head and neck squamous cell carcinoma (HNSCC) tissues using bioinformatics technology analysis, and to predict potential key genes. Methods　Related data from 19 cases of metastatic HNSCC and 48 cases of non-metastatic HNSCC with clear information were obtained from the Cancer Genome Atlas dataset. The upregulated and downregulated differentially expressed genes in metastatic and non-metastatic HNSCC tissues were screened using bioinformatics technology analysis. Subsequent analysis included cluster analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and gene onto-logy analysis. Results indicate that β-1,4-N-acetyl-galactosaminyltransferase (B4GALNT4) was selected as a key gene due to its smallest “adjusted P value.” This gene was verified at the cellular level using quantitative reverse transcription-polymerase chain reaction and Western Blot. Results　Compared with non-metastatic HNSCC tissues, 76 genes were significantly downregulated and 99 genes were significantly upregulated in the metastatic HNSCC tissues. Among which, the B4GALNT4 gene expression was found to be the most significantly upregulated. Cellular-level experiments revealed that, compared to UM-2 cells with weak metastasis capability, the mRNA and protein expression levels of B4GALNT4 in UM-1 cells with strong metastasis capability were significantly higher (P<0.05). In addition, the level of protein O-glycosylation in UM-1 cells was also significantly increased in UM-1 cells compared to UM-2 cells (P<0.05). Conclusion　B4GALNT4 is upregulated in metastatic HNSCC tissues and cells, and its expression is positively correlated with the level of protein glycosylation. Therefore, B4GALNT4 is a potentially new target for the prevention and treatment of tumor metastasis.

Key words: head and neck squamous cell carcinoma, metastasis, β-1,4-N-acetyl-galactosaminyltransferase, glycosylation

中图分类号: 

  • R739.8

表 1

样本的基线信息"

特征转移型（n=19）非转移型（n=48）
性别男1831
女117
年龄/岁61.264.3
吸烟是1136
否812
B4GALNT4表达水平高1612
低336
临床分期Ⅰ05
Ⅱ04
Ⅲ19
Ⅳ1830

表 2

qRT-PCR引物序列"

名称引物序列
B4GALNT4正向：5’-CTACGGGCGAGATGGTGAG-3’
反向：5’-CTCAGCCCTCTGTGTGGATG-3’
GAPDH正向：5’-GCAAGCACAGAGTTGGATGA-3’
反向：5’-CTGGCGTAGGGAGTTCAGAG-3’

图 1

转移型和非转移型HNSCC中的DEGA：DEG的火山图；B：前25个上调和下调DEG的热图。"

图 2

DEG的GO富集和KEGG通路分析A：上调DEG的GO富集分析；B：下调DEG的GO富集分析；C：上调DEG的KEGG通路分析；D：下调DEG的KEGG通路分析。"

图 3

B4GALNT4在HNSCC转移细胞系中的表达情况A：基因差异表达；B：mRNA的表达水平；C：蛋白表达水平；****：P<0.000 1；**：P<0.01；ns：差异无统计学意义。"

图 4

B4GALNT4与信号通路之间的相关性A：ECM降解信号通路；B：谷胱甘肽代谢信号通路；C：铁死亡信号通路；D：糖酵解/糖原异生信号通路；E：黏蛋白型O-聚糖的生物合成信号通路；F：甘露糖型O-聚糖的生物合成信号通路。"

图 5

HNSCC细胞系中蛋白O-糖基化的表达水平"

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