Prognostic and immunological role of sialyltransferase ST6GALNAC1 in head and neck squamous cell carcinoma

doi:10.3969/j.issn.1009-976X.2023.02.009

Abstract

Abstract: Objective To investigate the expression of ST6GALNAC1 and its prognostic and immunological value in HNSCC by bioinformatics analysis. Methods The transcriptome data of HNSCC were obtained from TCGA database and an R package Limma was used to screen abnormally expressed glycosyltransferase genes. UALCAN database was leveraged to investigate the correlation between ST6GALNAC1 expression levels and distinct clinical signatures. GEPIA2 website was used to conduct survival analysis. The correlation between ST6GALNAC1 expression levels and tumor-associated fibroblasts was explored by harnessing TIMER2.0 database. The R package IOBR was exploited to calculate the score of the immune infiltrating cells, and the Sangerbox tool was utilized to visualize the disparities in the expression levels of the checkpoint and HLA genes. ST6GALNAC1-related genes were enriched by STRING, GEPIA2, and Sangerbox. The WB and qRT-PCR were adopted to detect the expression of ST6GALNAC1.Results A glycosyltransferase ST6GALNAC1 was found significantly downregulated in HNSCC and its expression levels were associated with tumor clinical pathology grade, age, and lymph node metastasis of HNSCC patients （P<0.05）. Patients with low expression of ST6GALNAC1 have substantially shorter overall survival（OS）and progression-free survival（DFS）（P<0.05）. The ST6GALNAC1 expression was negatively correlated with immune cell infiltration in tumor tissue, expression of immune checkpoint genes and HLA genes. GO and KEGG analysis revealed that ST6GALNAC1 genes were mainly involved in the biosynthesis of glycoproteins. The experiment results showed us the decreased expression of ST6GALNAC1 in Cal27 cells. Conclusion Sialyltransferase ST6GALNAC1 was down-regulated in HNSCC, which may be associated with inferior outcomes and immune infiltration of HNSCC patients. The expression of ST6GALNAC1 was down-regulated in Cal27 cells. ST6GALNAC1 may be a novel therapeutic target for HNSCC.

Key words: glycosyltransferase, head and neck squamous cell carcinoma, prognosis, immune infiltration, bioinformatic analysis

摘要： 目的本研究旨在利用生物信息学分析方法探讨ST6GALNAC1在头颈部鳞状细胞癌（HNSCC）中的表达及其预后和免疫学价值。方法从TCGA数据库中获取HNSCC的转录组数据,使用R软件Limma包筛选糖基转移酶差异基因。通过UALCAN和HPA数据库对ST6GALNAC1进行表达分析。用UALCAN数据库分析ST6GALNAC1表达与不同临床特征的相关性。通过GEPIA2可视化网站进行生存分析。通过TIMER2.0数据库进行ST6GALNAC1表达与肿瘤相关成纤维细胞的相关性分析。使用R软件包IOBR计算免疫浸润细胞评分,用Sangerbox工具对免疫检查点基因和HLA基因的表达差异进行可视化。通过STRING、GEPIA2和Sangerbox工具进行ST6GALNAC1相关基因的富集分析。利用WB和q-PCR检测人舌鳞癌细胞系Cal27的ST6GALNAC1表达水平。结果从TCGA数据库中筛选出HNSCC糖基转移酶差异基因ST6GALNAC1。在HNSCC中,ST6GALNAC1表达显著下调（P<0.05）。ST6GALNAC1表达与HNSCC患者的肿瘤分级、年龄、淋巴结转移状况存在相关关系（P<0.05）。ST6GALNAC1低表达组患者的总体生存期（OS）和无进展生存期（DFS）显著缩短（P<0.05）。ST6GALNAC1表达与肿瘤组织的免疫细胞浸润、免疫检查点基因和HLA基因的表达呈负相关性。GO和KEGG分析显示ST6GALNAC1相关基因主要参与糖蛋白的生物合成过程。实验结果显示,Cal27细胞的ST6GALNAC1蛋白和mRNA表达水平下降。结论 ST6GALNAC1在HNSCC中表达下调,与HNSCC患者预后不良、肿瘤微环境免疫细胞浸润相关。ST6GALNAC1在Cal27细胞中表达下调。ST6GALNAC1有望成为新的HNSCC治疗靶点。

关键词: 糖基转移酶, 头颈部鳞状细胞癌, 预后, 免疫浸润, 生物信息学

CLC Number:

R739.6

WU Kang-xiu, LI Zhi-guo, LIU Sui-ping, SU Hong-jun, XIONG Min-min. Prognostic and immunological role of sialyltransferase ST6GALNAC1 in head and neck squamous cell carcinoma[J]. Lingnan Modern Clinics In Surgery, 2023, 23(02): 152-161.

吴康秀, 黎志国, 刘穗萍, 苏鸿君, 熊敏敏. 唾液酸转移酶ST6GALNAC1在头颈部鳞状细胞癌中的表达及其预后和免疫学价值[J]. 岭南现代临床外科, 2023, 23(02): 152-161.

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