Zhu Lixin, Duan Wenliang, Peng Lijing, Shan Xinxin, Liu Yuan, Huang Zhenke, Da Yunxiang, Han Yanyan
Department of Otolaryngology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, China.
Department of Otolaryngology, Shanghai Punan Hospital, Shanghai, 200120, China.
Heliyon. 2024 Sep 18;10(19):e37897. doi: 10.1016/j.heliyon.2024.e37897. eCollection 2024 Oct 15.
Nasopharyngeal carcinoma (NPC) is a highly diverse and aggressive cancer type, leading to varying prognoses and responses to immunotherapy. This study aims to develop a protein-based signature that provides new insights into assessing the prognosis and immunotherapeutic response in NPC patients.
We obtained transcriptomic and proteomic data for NPC from TCGA and CPTAC databases, respectively. Differentially expressed proteins with prognostic significance were identified using limma combined with uniCox analysis. A prognostic protein signature was created utilizing the LASSO algorithm. Receiver operating characteristic (ROC) curve analysis along with Kaplan-Meier survival analysis was conducted to assess the predictive accuracy of this signature. To evaluate immune infiltration levels among patients categorized by high or low risk scores (RPscores), we employed ssGSEA and ESTIMATE methods, while TIDE was used to forecast responses to immunotherapy. Our research pinpointed four critical prognostic proteins: CdSTA, AGR3, DUSP14, and LRRC17, allowing us to compute risk scores (RPscores). Kaplan-Meier curves demonstrated that individuals in the low-risk category exhibited better survival rates. Furthermore, RPscore effectively predicted overall survival across both training and testing cohorts. The ssGSEA results indicated that RPscore is linked with an immune-suppressive microenvironment correlating with diminished immune responses. Notably, DUSP14 showed significant upregulation in NPC cases; its role in promoting cell invasion and metastasis was confirmed through in vitro studies.
We have established a robust protein-related signature capable of accurately forecasting prognosis as well as immunotherapy outcomes for NPC patients. Moreover, DUSP14 emerged as a potential therapeutic target due to its strong association with patient prognosis in nasopharyngeal carcinoma.
鼻咽癌（NPC）是一种高度异质性且侵袭性强的癌症类型，导致预后和对免疫治疗的反应各不相同。本研究旨在开发一种基于蛋白质的特征，为评估鼻咽癌患者的预后和免疫治疗反应提供新的见解。
我们分别从TCGA和CPTAC数据库中获取了鼻咽癌的转录组和蛋白质组数据。使用limma结合单因素Cox分析鉴定具有预后意义的差异表达蛋白。利用LASSO算法创建了一个预后蛋白质特征。进行受试者工作特征（ROC）曲线分析以及Kaplan-Meier生存分析，以评估该特征的预测准确性。为了评估高风险或低风险评分（RP评分）分类患者中的免疫浸润水平，我们采用了单样本基因集富集分析（ssGSEA）和ESTIMATE方法，同时使用肿瘤免疫功能障碍和排除（TIDE）来预测对免疫治疗的反应。我们的研究确定了四种关键的预后蛋白：CdSTA、AGR3、DUSP14和LRRC17，从而能够计算风险评分（RP评分）。Kaplan-Meier曲线表明，低风险组个体的生存率更高。此外，RP评分有效地预测了训练和测试队列中的总生存期。ssGSEA结果表明，RP评分与免疫抑制微环境相关，与免疫反应减弱有关。值得注意的是，DUSP14在鼻咽癌病例中显著上调；通过体外研究证实了其在促进细胞侵袭和转移中的作用。
我们建立了一个强大的蛋白质相关特征，能够准确预测鼻咽癌患者的预后以及免疫治疗结果。此外，由于DUSP14与鼻咽癌患者预后密切相关，它成为了一个潜在的治疗靶点。
