背景:头颈部鳞状细胞癌(HNSCC)是一种死亡率很高的恶性肿瘤,大量研究证实了炎症与恶性肿瘤之间的相关性以及炎症相关调节因子参与HNSCC的进展。然而,尚未建立基于与炎症因子有关的基因的HNSCC预后模型。方法:首先,我们从TCGA和GEO(GSE41613)下载了头颈部鳞状细胞癌患者的转录组数据和临床信息进行数据分析,模型构建,和差异基因表达分析,分别。从已发表的论文中筛选与炎症因子相关的基因,并与差异表达的基因相交,以鉴定差异表达的炎症因子相关基因。然后根据差异表达的炎症因子相关基因对亚组进行分型。单变量,随后应用LASSO和多变量Cox回归算法来鉴定与炎症因子相关的预后基因并构建预后预测模型。通过Kaplan-Meier生存分析和受试者工作特征曲线(ROC)评估模型的预测性能。随后,我们通过免疫浸润分析了高危组和低危组患者之间免疫组成的差异。还基于GSCALite数据库分析了模型基因与药物敏感性(GSDC和CTRP)之间的相关性。最后,我们检查了病理组织中预后基因的表达,验证这些基因可用于预测预后。结果:使用单变量,拉索,和多元cox回归分析,我们基于与炎症因子相关的13个基因(ITGA5,OLR1,CCL5,CXCL8,IL1A,SLC7A2,SCN1B,RGS16,TNFRSF9,PDE4B,NPFFR2、OSM、ROS1)。在训练集和验证集上,低危组HNSCC患者的总生存期(OS)均明显优于高危组。通过聚类,我们确定了HNSCC癌的三种分子亚型(C1,C2和C3),C1亚型的OS明显优于C2和C3亚型。ROC分析表明,我们的模型对HNSCC患者具有精确的预测能力。富集分析显示,高危组和低危组表现出较强的免疫功能差异。CIBERSORT免疫浸润评分显示25个相关和差异表达的炎症因子基因均与免疫功能相关。随着风险分数的增加,肿瘤组织中特异性免疫功能激活降低,这与不良预后有关。我们还筛选了高风险和低风险组之间的易感性,并显示高风险组中的患者对他拉唑帕尼-1259,喜树碱-1003,长春新碱-1818,Azd5991-1720,替尼泊苷-1809和Nutlin-3a(-)-1047更敏感。最后,我们检查了OLR1,SCN1B,和PDE4B基因在HNSCC病理组织中的表达,并验证了这些基因可用于预测HNSCC的预后。结论:在本实验中,我们提出了基于炎症相关因素的HNSCC预后模型。它是一种非侵入性基因组表征预测方法,在预测患者生存结果和治疗反应方面表现出令人满意和有效的性能。未来将探索更多结合医学和电子的跨学科领域。
Background: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor with a very high mortality rate, and a large number of studies have confirmed the correlation between inflammation and malignant tumors and the involvement of inflammation-related regulators in the progression of HNSCC. However, a prognostic model for HNSCC based on genes involved in inflammatory factors has not been established. Methods: First, we downloaded transcriptome data and clinical information from patients with head and neck squamous cell carcinoma from TCGA and GEO (GSE41613) for data analysis, model construction, and differential gene expression analysis, respectively. Genes associated with inflammatory factors were screened from published papers and intersected with differentially expressed genes to identify differentially expressed inflammatory factor-related genes. Subgroups were then typed according to differentially expressed inflammatory factor-related genes. Univariate, LASSO and multivariate Cox regression algorithms were subsequently applied to identify prognostic genes associated with inflammatory factors and to construct prognostic prediction models. The predictive performance of the model was evaluated by Kaplan-Meier survival analysis and receiver operating characteristic curve (ROC). Subsequently, we analyzed differences in immune composition between patients in the high and low risk groups by immune infiltration. The correlation between model genes and drug sensitivity (GSDC and CTRP) was also analyzed based on the GSCALite database. Finally, we examined the expression of prognostic genes in pathological tissues, verifying that these genes can be used to predict prognosis. Results: Using univariate, LASSO, and multivariate cox regression analyses, we developed a prognostic risk model for HNSCC based on 13 genes associated with inflammatory factors (ITGA5, OLR1, CCL5, CXCL8, IL1A, SLC7A2, SCN1B, RGS16, TNFRSF9, PDE4B, NPFFR2, OSM, ROS1). Overall survival (OS) of HNSCC patients in the low-risk group was significantly better than that in the high-risk group in both the training and validation sets. By clustering, we identified three molecular subtypes of HNSCC carcinoma (C1, C2, and C3), with C1 subtype having significantly better OS than C2 and C3 subtypes. ROC analysis suggests that our model has precise predictive power for patients with HNSCC. Enrichment analysis showed that the high-risk and low-risk groups showed strong immune function differences. CIBERSORT immune infiltration score showed that 25 related and differentially expressed inflammatory factor genes were all associated with immune function. As the risk score increases, specific immune function activation decreases in tumor tissue, which is associated with poor prognosis. We also screened for susceptibility between the high-risk and low-risk groups and showed that patients in the high-risk group were more sensitive to talazoparib-1259, camptothecin-1003, vincristine-1818, Azd5991-1720, Teniposide-1809, and Nutlin-3a (-) -1047.Finally, we examined the expression of OLR1, SCN1B, and PDE4B genes in HNSCC pathological tissues and validated that these genes could be used to predict the prognosis of HNSCC. Conclusion: In this experiment, we propose a prognostic model for HNSCC based on inflammation-related factors. It is a non-invasive genomic characterization prediction method that has shown satisfactory and effective performance in predicting patient survival outcomes and treatment response. More interdisciplinary areas combining medicine and electronics will be explored in the future.