He Siyi, Meng Jiali, Liang Chunyan, Wang Yiru, Qin Xinling, Huang Lulu, Wang Rensheng, Huang Weimei
Department of Radiation Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Rd, Nanning, 530021, Guangxi, China.
Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, 530021, Guangxi, China.
Discov Oncol. 2025 Mar 31;16(1):430. doi: 10.1007/s12672-025-02214-x.
The incidence of head and neck squamous cell carcinoma (HNSCC) remains high, accompanied by low 5-year survival rates. Identifying prognostic factors is essential for advancing personalized treatment approaches. Increasing evidence implicates aberrant alternative splicing (AS) plays a key role in tumor progression. Utilizing data from TCGA and TCGA SpliceSeq, prognosis-associated AS events were identified through Cox regression analysis. A prognostic risk model was developed via multivariate Cox and LASSO regression, with validation conducted using Kaplan-Meier survival analysis and ROC curve analysis. The correlation between splicing factors (SFs) and prognosis-associated AS events was analyzed using Pearson's method, followed by the construction of an SF-AS regulatory network. Key splicing factors (KSFs) were identified using Cytoscape software. Expression of KSFs in HNSCC was confirmed by quantitative PCR and Western blotting. SiRNA-mediated knockdown in HNSCC cell lines (HONE1, HN4, SAS) demonstrated effects on cell proliferation, invasion, and migration, as assessed by CCK8, colony formation, Transwell, and wound healing assays. Tumor growth was further evaluated in a subcutaneous tumor model in vivo. A total of 2347 survival-related AS events were identified, of which eleven were used to construct the prognostic model. Patients in the low-risk group exhibited significantly improved outcomes (P = 0e + 00), underscoring the model's predictive accuracy. Notably, DDX39B and PRPF39 emerged as key splicing factors, exhibiting high expression in HNSCC and correlating with poor prognosis, positioning them as potential biomarkers and therapeutic targets.
头颈部鳞状细胞癌（HNSCC）的发病率仍然很高，5年生存率较低。识别预后因素对于推进个性化治疗方法至关重要。越来越多的证据表明异常可变剪接（AS）在肿瘤进展中起关键作用。利用来自TCGA和TCGA SpliceSeq的数据，通过Cox回归分析确定了与预后相关的AS事件。通过多变量Cox和LASSO回归建立了预后风险模型，并使用Kaplan-Meier生存分析和ROC曲线分析进行验证。使用Pearson方法分析剪接因子（SFs）与预后相关AS事件之间的相关性，随后构建SF-AS调控网络。使用Cytoscape软件识别关键剪接因子（KSFs）。通过定量PCR和蛋白质印迹法证实了HNSCC中KSFs的表达。在HNSCC细胞系（HONE1、HN4、SAS）中，通过CCK8、集落形成、Transwell和伤口愈合试验评估，siRNA介导的敲低显示对细胞增殖、侵袭和迁移有影响。在体内皮下肿瘤模型中进一步评估肿瘤生长。共鉴定出2347个与生存相关的AS事件，其中11个用于构建预后模型。低风险组患者的预后显著改善（P = 0e + 00），突出了该模型的预测准确性。值得注意的是，DDX39B和PRPF39成为关键剪接因子，在HNSCC中高表达且与不良预后相关，使其成为潜在的生物标志物和治疗靶点。
