He Miao, Wang Li, Yue Zihan, Feng Chunbo, Dai Guosheng, Jiang Jinsong, Huang Hui, Ji Qingjun, Zhou Minglang, Li Dapeng, Chai Wei
Department of Otorhinolaryngology, Head and Neck Surgery, The People’s Hospital of Bozhou, Bozhou 236000, Anhui, China.
Scientific Research and Experiment Center, The People’s Hospital of Bozhou, Bozhou 236000, Anhui, China.
Aging (Albany NY). 2024 Jan 19;16(2):1750-1766. doi: 10.18632/aging.205455.
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous cancer characterized by difficulties in early diagnosis and outcome prediction. Aberrant glycosylated structures produced by the aberrant expression of glycosyltransferases are prevalent in HNSCC. In this study, we aim to construct glycosyltransferase-related gene signatures with diagnostic and prognostic value to better stratify patients with HNSCC and improve their diagnosis and prognosis.
Bioinformatic tools were used to process data of patients with HNSCC from The Cancer Genome Atlas (TCGA) database. The prognostic model was formatted using univariate and multivariate Cox regression methods, while the diagnostic signature was constructed using support vector machine (SVM) and LASSO analysis. The results were verified using the Gene Expression Omnibus (GEO) cohort. The tumor microenvironment and benefits of immune checkpoint inhibitor (ICI) therapy in subgroups defined by glycosyltransferase-related genes were analyzed. Molecular biology experiments, including western blotting, cell counting kit (CCK)-8, colony formation, wound healing, and Transwell assays, were conducted to confirm the oncogenic function of beta-1,4-galactosyltransferase 3 (B4GALT3) in HNSCC.
We established a five-gene prognostic signature and a 15-gene diagnostic model. Based on the median risk score, patients with low risk had longer overall survival than those in the high-risk group, which was consistent with the results of the GEO cohort. The concrete results suggested that high-risk samples were related to a high tumor protein (TP)53 mutation rate, high infiltration of resting memory cluster of differentiation (CD)4 T cells, resting natural killer (NK) cells, and M0 macrophages, and benefited from ICI therapy. In contrast, the low-risk subgroup was associated with a low TP53 mutation rate; and high infiltration of naive B cells, plasma cells, CD8 T cells, and resting mast cells; and benefited less from ICI therapy. In addition, the diagnostic model had an area under curve (AUC) value of 0.997 and 0.978 in the training dataset and validation cohort, respectively, indicating the high diagnostic potential of the model. Ultimately, the depletion of B4GALT3 significantly hindered the proliferation, migration, and invasion of HNSCC cells.
We established two new biomarkers that could provide clinicians with diagnostic, prognostic, and treatment guidance for patients with HNSCC.
头颈部鳞状细胞癌（HNSCC）是一种高度异质性的癌症，其特征在于早期诊断和预后预测存在困难。糖基转移酶异常表达产生的异常糖基化结构在HNSCC中普遍存在。在本研究中，我们旨在构建具有诊断和预后价值的糖基转移酶相关基因特征，以更好地对HNSCC患者进行分层，并改善其诊断和预后。
使用生物信息学工具处理来自癌症基因组图谱（TCGA）数据库的HNSCC患者数据。使用单变量和多变量Cox回归方法构建预后模型，同时使用支持向量机（SVM）和LASSO分析构建诊断特征。使用基因表达综合数据库（GEO）队列验证结果。分析了由糖基转移酶相关基因定义的亚组中的肿瘤微环境和免疫检查点抑制剂（ICI）治疗的益处。进行了包括蛋白质免疫印迹、细胞计数试剂盒（CCK）-8、集落形成、伤口愈合和Transwell实验在内的分子生物学实验，以证实β-1,4-半乳糖基转移酶3（B4GALT3）在HNSCC中的致癌作用。
我们建立了一个五基因预后特征和一个15基因诊断模型。根据中位风险评分，低风险患者的总生存期长于高风险组患者，这与GEO队列的结果一致。具体结果表明，高风险样本与高肿瘤蛋白（TP）53突变率、静息记忆分化簇（CD）4 T细胞、静息自然杀伤（NK）细胞和M0巨噬细胞的高浸润有关，并从ICI治疗中获益。相比之下，低风险亚组与低TP53突变率相关；幼稚B细胞、浆细胞、CD8 T细胞和静息肥大细胞的高浸润；以及从ICI治疗中获益较少。此外，诊断模型在训练数据集和验证队列中的曲线下面积（AUC）值分别为0.997和0.978，表明该模型具有较高的诊断潜力。最终，B4GALT3的缺失显著阻碍了HNSCC细胞的增殖、迁移和侵袭。
我们建立了两种新的生物标志物，可为HNSCC患者的临床诊断、预后和治疗提供指导。
