基于肿瘤微环境相关的HPV阴性头颈鳞状细胞癌预后风险评分模型的构建与评估

Construction and evaluation of prognostic risk scoring model based on tumor microenvironment of HPV-negative head and neck squamous cell carcinoma

目的通过生物信息学方法构建人乳头瘤病毒(human papillomavirus,HPV)阴性头颈鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)肿瘤微环境(tumor microenvironment,TME)相关的预后风险评分模型。方法根据HPV阴性HNSCC患者免疫、基质评分中位数分组,并筛选影响HPV阴性HNSCC预后的TME相关基因。将TCGA数据库HPV阴性HNSCC患者按3∶1比例分为训练组和测试组,在训练组内通过Lasso回归算法建立预后风险评分模型。利用Kaplan-Meier生存曲线和ROC曲线对模型进行评估。测试组和GEO数据库分别对模型进行内部验证和外部验证。通过Pearson相关性分析和GSVA分析探讨模型与免疫细胞浸润水平的关系。结果筛选出241个与HPV阴性HNSCC患者TME相关预后基因。构建并验证了包括ABCB1、C13orf18、CCL21、CCR7、CD79a、CSF2RB、DPT、IL10和SFRP1在内的TME相关基因预后评分模型。预后低风险评分的HPV阴性HNSCC患者呈现高免疫细胞浸润水平。结论构建并验证了TME相关HPV阴性HNSCC预后风险评分模型,该模型可作为潜在的预后生物标志物,并有助于指导HPV阴性HNSCC患者个性化治疗。

Objective To construct a prognostic risk scoring model related to tumor microenvironment(TME) of human papillomavirus(HPV)-negative head and neck squamous cell carcinoma(HNSCC) via bioinformatics methods.Methods Patients were divided according to the median value of immune and stromal scores and TME-related genes that affected the prognosis of HPV-negative HNSCC were screened.The patients in TOGA database were randomly divided into training group and testing group at 3:1,and the prognostic risk scoring model was established through Lasso algorithm in the training group.Kaplan-Meier method and ROC curve were used to evaluate the model.The testing group and GEO cohort were used for internal verification and external verification.The Pearson correlation analysis and GSVA analysis were used to explore the relationship between this model and the level of immune cell infiltration.Results Totally 241 prognostic genes related to TME were screened in HPV-negative HNSCC patients.TME-related gene prognostic scoring model,including ABCB1,C13 orf18,CCL21,CCR7,CD79 a,CSF2 RB,DPT,IL10 and SFRP1 was constructed and verified.Low-risk scores indicated a high level of immune cell infiltration in HPV-negative HNSCC.Conclusion A TMErelated gene prognostic scoring model is constructed and verified,which may serve as a potential prognostic biomarker and guide personalized treatment for HPV-negative HNSCC.