关键词: 头颈部鳞状细胞癌, 外生骨疣蛋白2, 突变, 预后

Abstract: Objective    To preliminarily explore the gene mutation and expression characteristics of exostosin glycosyltransferase 2（EXT2）in head and neck squamous cell carcinoma（HNSCC）and its impact on clinical prognosis. Methods    A total of 20 HNSCC patients who underwent next-generation sequencing at the Stomatological Hospital Affiliated to China Medical University from January 2015 to January 2024 were selected. Mutant genes detected in ≥ 2 cases were regarded as target genes for analysis in the cancer genome atlas（TCGA）database. RNA-seq was used to detect the relative expression level of EXT2 in tumor tissues of 20 HNSCC patients. The patients were divided into the EXT2 high-expression group（relative expression level > median）and the EXT2 low-expression group（relative expression level ≤ median），and the prognosis of the two groups was compared and analyzed. In the TCGA public database，the expression difference of target genes between tumor tissues and adjacent normal tissues of 503 HNSCC patients and its impact on prognosis were compared. The single-sample gene set enrichment analysis algorithm was used to calculate the infiltration scores of 24 types of immune cells in the HNSCC tumor microenvironment and their correlation with EXT2 expression. The impact of EXT2 expression on the prognosis of 33 types of tumors was analyzed. Results    Among the 20 HNSCC patients，gene mutations were detected in 11 cases，with a total of 62 mutant genes，including 13 target genes（mutant genes detected in ≥ 2 cases）. Among them，point mutations in the EXT2 gene were detected in 2 male patients with stage Ⅳ poorly differentiated HNSCC. EXT2 gene mutation had a significant impact on the progression-free survival of patients（χ2 = 15.000，P < 0.001）. The progression-free survival of the EXT2 high-expression group was significantly shorter than that of the low-expression group，and the difference was statistically significant（χ2 = 9.210，P = 0.002）. Analysis based on the TCGA database showed that among the target genes，the relative expression levels of EXT2，BRCA1- associated protein 1（BAP1），FAT atypical cadherin 1（FAT1），cylindromatosis protein（CYLD），Janus kinase 1（JAK1），meiotic recombination 11 homolog（MRE11），nuclear factor kappa-B inhibitor alpha（NFKBIA），ROS proto-oncogene 1（ROS1），and septin 9（SEPTIN9）in tumor tissues were higher than those in adjacent normal tissues，and the differences were statistically significant（all P < 0.05）. Among them，only high EXT2 expression was a risk factor for patient prognosis（HR = 1.444，95%CI：1.104 - 1.890，P = 0.007）. In the HNSCC tumor microenvironment，high EXT2 expression was positively correlated with the infiltration scores of macrophages，neutrophils，and natural killer cells，and negatively correlated with the infiltration scores of B cells，CD8+ T cells，and cytotoxic cells（all P < 0.05）. High EXT2 expression was a risk factor for the prognosis of patients with HNSCC，bladder urothelial carcinoma，low-grade glioma of head，hepatocellular carcinoma，mesothelioma，and sarcoma（all HR > 1.000，P < 0.05）. Conclusion    EXT2 gene mutation and expression are closely related to the prognosis of HNSCC. It may affect the development of various tumors by remodeling the immunosuppressive microenvironment and has the potential to be a biomarker for predicting the prognosis of HNSCC.

Key words: head and neck squamous cell carcinoma, HNSCC；exostosin glycosyltransferase 2, EXT2；mutation；prognosis