Zhang Jianguo, Zhang Jianzhong, Yuan Cheng, Luo Yuan, Li Yangyi, Dai Panpan, Sun Wenjie, Zhang Nannan, Ren Jiangbo, Zhang Junhong, Gong Yan, Xie Conghua
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071 Hubei China.
Department of Occupational and Environmental Health, School of Public Health, Qingdao University, Dengzhou Road 38, Qingdao, 266021 China.
Cancer Cell Int. 2020 Jul 20;20:330. doi: 10.1186/s12935-020-01429-y. eCollection 2020.
The incidence of lung squamous cell carcinoma (LUSC) increased substantially in recent years. Systematical investigation of the immunogenomic pattern is critical to improve the prognosis of LUSC.
Based on the TCGA and GEO dataset, we integrated the immune-related genes (IRGs) expression profile and the overall survival (OS) of 502 patients with LUSC. The survival-related and differentially-expressed IRGs in LUSC patients were evaluated by univariate cox regression and LASSO regression analysis. By applying multivariate cox analysis, a new prognostic indicator based on IRGs was established. We also used CIBERSORT algorithms and TIMER database to analyze immune infiltration of LUSC. Both gene set enrichment analysis (GSEA) and principal component analysis (PCA) was carried out for functional annotation. With the assist of computational biology, we also investigated the latent properties and molecular mechanisms of these LUSC-specific IRGs. We analyzed the correlation between immune checkpoints and risk score.
A novel prognostic model was established based on 11 IRGS, including CXCL5, MMP12, PLAU, ELN, JUN, RNASE7, JAG1, SPP1, AGTR2, FGFR4, and TNFRSF18. This model performed well in the prognostic forecast, and was also related to the infiltration of immune cells. Besides, the high-risk groups and the low-risk groups exhibited distinct layout modes in PCA analysis, and GSEA results showed that different immune status among these groups.
In summary, our researches screened out clinically significant IRGs and proved the significance of IRG-based, individualized immune-related biomarkers in monitoring, prognosis, and discern of LUSC.
近年来肺鳞状细胞癌(LUSC)的发病率大幅上升。系统研究免疫基因组模式对于改善LUSC的预后至关重要。
基于TCGA和GEO数据集,我们整合了502例LUSC患者的免疫相关基因(IRGs)表达谱和总生存期(OS)。通过单变量cox回归和LASSO回归分析评估LUSC患者中与生存相关且差异表达的IRGs。通过多变量cox分析,建立了基于IRGs的新预后指标。我们还使用CIBERSORT算法和TIMER数据库分析LUSC的免疫浸润情况。进行了基因集富集分析(GSEA)和主成分分析(PCA)以进行功能注释。借助计算生物学,我们还研究了这些LUSC特异性IRGs的潜在特性和分子机制。我们分析了免疫检查点与风险评分之间的相关性。
基于11个IRGs建立了一种新的预后模型,包括CXCL5、MMP12、PLAU、ELN、JUN、RNASE7、JAG1、SPP1、AGTR2、FGFR4和TNFRSF18。该模型在预后预测中表现良好,并且还与免疫细胞浸润有关。此外,高危组和低危组在PCA分析中表现出不同的布局模式,GSEA结果显示这些组之间存在不同的免疫状态。
总之,我们的研究筛选出了具有临床意义的IRGs,并证明了基于IRG的个体化免疫相关生物标志物在LUSC监测、预后和鉴别中的重要性。