基于癌症基因组图谱肺鳞状细胞癌免疫细胞浸润图景及预后分析

目的 探讨肺鳞状细胞癌组织免疫细胞浸润全景,构建预后风险评估模型,分析并评估患者的预后.方法 利用癌症基因组图谱(TCGA)数据库肺鳞状细胞癌全转录组数据,通过R 4.0.3软件利用CIBERSORT反卷积算法计算不同免疫细胞浸润相对含量,用单因素和多因素Cox回归分析建立预后风险评估模型,并用ROC曲线评估模型效能,结合临床变量绘制预测患者3、5、10年生存率列线图.结果 共涉及22种免疫细胞类型.正常组织中的8种免疫细胞亚群(初始B细胞、浆细胞、激活记忆CD4T细胞、滤泡辅助性T细胞、调节性T细胞、M0型巨噬细胞、M1型巨噬细胞、休眠树突状细胞)浸润相对含量均低于肺鳞状细胞癌组织(P＜0.05或P＜0.01),正常组织中的另外8种免疫细胞亚群休眠记忆CD4T细胞、休眠自然杀伤(NK)细胞、单核细胞、M2型巨噬细胞、激活树突状细胞、休眠肥大细胞、嗜酸性粒细胞、中性粒细胞]浸润相对含量均高于肺鳞状细胞癌组织(P＜0.01或P＜0.05),其余免疫细胞亚群(记忆性B细胞、CD8T细胞、初始CD4T细胞、γ/δT细胞,激活NK细胞、激活肥大细胞)在两组间差异均无统计学意义(P均＞0.05).初始CD4T细胞、休眠记忆CD4T细胞对肺鳞状细胞癌患者是危险因素(HR＞1),而激活记忆CD4T细胞、滤泡辅助性T细胞、休眠树突状细胞则是保护因素(HR＜1).激活记忆CD4 T细胞、休眠树突状细胞浸润相对含量高的肺鳞状细胞癌患者预后较相对含量低的患者好(P＜0.05).用激活记忆CD4T细胞、滤泡辅助性T细胞、休眠树突状细胞构建的肺鳞状细胞癌患者预后风险评估模型的效能良好,ROC曲线的AUC为0.678.结论 休眠树突状细胞、激活记忆CD4T细胞与肺鳞状细胞癌的发生、预后有关,并且可以作为独立的预后因子.预后相关免疫细胞亚群构建的预后风险评估模型效能良好.

The infiltration of immune cells in lung squamous cell carcinoma and its prognostic analysis based on The Cancer Genome Atlas

Objective: To investigate the proportion of 22 immune cells infiltration in lung squamous carcinoma (LSC) and establish a prognostic risk assessment model to assess the prognosis of patients. Methods: Based on the data sets of lung squamous cell carcinoma from The Cancer Genome Atlas (TCGA) database, R software and CIBERSORT deconvolution algorithm were used to calculate the proportion of 22 immune cells infiltration. Via univariate and multivariate COX analysis, we constructed prognostic risk assessment model. Results: In normal tissues 8 immune cells subsets was significantly lower than that in lung squamous carcinoma tissues (P < 0.05). While other 8 immune cells subsets are opposite (P < 0.05). There was no statistically significant difference in the remaining immune cell subsets. CD4 T cells naive and T cells CD4 memory activated were positively correlated with survival in patients with lung squamous cell carcinoma, while T cells CD4 memory activated, T cells helper follicular, and dendritic cells resting were negatively correlated with overall survival in patients with lung squamous cell carcinoma. T cells CD4 memory activated, T cells helper follicular, and dendritic cells resting were used to construct a prognostic risk assessment model. Conclusion: Immune cells are associated with tumorigenesis and prognosis, and the proportion of 22 immune cells infiltration is an essential characteristic of tumor tissues, representing individual differences. Dendritic cells resting, T cells CD4 memory activated associated with the occurrence, progress and prognosis of lung squamous carcinoma and can be used as an independent prognostic factor. Our study will contribute to understand the landscape of immune cell infiltration and assess the prognosis of patients and help to explore the mechanism of immune cell recruitment.