Ye Fan, Wu Pingan, Zhu Yaqiong, Huang Guan, Tao Ying, Liao Zhencheng, Guan Yafeng
Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Department of Otolaryngology Head and Neck Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China.
Front Genet. 2022 Oct 21;13:989081. doi: 10.3389/fgene.2022.989081. eCollection 2022.
Head and neck squamous cell carcinoma (HNSC) is a prevalent and heterogeneous malignancy with poor prognosis and high mortality rates. There is significant evidence of alternative splicing (AS) contributing to tumor development, suggesting its potential in predicting prognosis and therapeutic efficacy. This study aims to establish an AS-based prognostic signature in HNSC patients. The expression profiles and clinical information of 486 HNSC patients were downloaded from the TCGA database, and the AS data were downloaded from the TCGA SpliceSeq database. The survival-associated AS events were identified by conducting a Cox regression analysis and utilized to develop a prognostic signature by fitting into a LASSO-regularized Cox regression model. Survival analysis, univariate and multivariate Cox regression analysis, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the signature and an independent cohort was used for validation. The immune cell function and infiltration were analyzed by CIBERSORT and the ssGSEA algorithm. Univariate Cox regression analysis identified 2726 survival-associated AS events from 1714 genes. The correlation network reported DDX39B, PRPF39, and ARGLU1 as key splicing factors (SF) regulating these AS events. Eight survival-associated AS events were selected and validated by LASSO regression to develop a prognostic signature. It was confirmed that this signature could predict HNSC outcomes independent of other variables multivariate Cox regression analysis. The risk score AUC was more than 0.75 for 3 years, highlighting the signature's prediction capability. Immune infiltration analysis reported different immune cell distributions between the two risk groups. The immune cell content was higher in the high-risk group than in the low-risk group. The correlation analysis revealed a significant correlation between risk score, immune cell subsets, and immune checkpoint expression. The prognostic signature developed from survival-associated AS events could predict the prognosis of HNSC patients and their clinical response to immunotherapy. However, this signature requires further research and validation in larger cohort studies.
头颈部鳞状细胞癌（HNSC）是一种常见的异质性恶性肿瘤，预后较差，死亡率较高。有大量证据表明可变剪接（AS）有助于肿瘤发展，提示其在预测预后和治疗效果方面的潜力。本研究旨在建立基于AS的HNSC患者预后特征。从TCGA数据库下载了486例HNSC患者的表达谱和临床信息，并从TCGA SpliceSeq数据库下载了AS数据。通过进行Cox回归分析确定与生存相关的AS事件，并将其用于通过拟合LASSO正则化Cox回归模型来建立预后特征。进行生存分析、单因素和多因素Cox回归分析以及受试者工作特征（ROC）曲线分析以评估该特征，并使用一个独立队列进行验证。通过CIBERSORT和ssGSEA算法分析免疫细胞功能和浸润情况。单因素Cox回归分析从1714个基因中鉴定出2726个与生存相关的AS事件。相关网络报道DDX39B、PRPF39和ARGLU1是调节这些AS事件的关键剪接因子（SF）。通过LASSO回归选择并验证了8个与生存相关的AS事件，以建立预后特征。经多因素Cox回归分析证实，该特征可独立于其他变量预测HNSC的预后。风险评分的3年AUC大于0.75，突出了该特征的预测能力。免疫浸润分析报告了两个风险组之间不同的免疫细胞分布。高风险组的免疫细胞含量高于低风险组。相关性分析揭示了风险评分、免疫细胞亚群和免疫检查点表达之间存在显著相关性。从与生存相关的AS事件中开发的预后特征可以预测HNSC患者的预后及其对免疫治疗的临床反应。然而，该特征需要在更大规模的队列研究中进一步研究和验证。
