三级淋巴结构评分在头颈部鳞状细胞癌预后评估及靶向治疗中的作用分析OA
Role of TLS score in prognosis evaluation and targeted therapy of head and neck squamous cell carcinoma
目的 基于生物信息学方法探讨三级淋巴结构(TLS)在头颈部鳞状细胞癌(HNSCC)中的免疫功能特征及其对患者预后评估的价值,并分析其与肿瘤免疫微环境及突变特征的关系,为 HNSCC 治疗策略制定提供参考.方法 通过 TCGA 数据库获取 HNSCC 患者(522 个肿瘤组织样本和 44 个正常对照组织样本)转录组数据及临床资料,筛选 TLS 相关基因并采用单样本基因集富集分析(ssGSEA)计算 TLS 评分,根据 TLS 评分的最佳截断值(Cut-off)将患者分为高评分 TLS 和低评分 TLS.比较不同评分患者总生存率,并采用单因素及多因素 Cox 回归分析评估TLS 评分的预后价值.进一步筛选不同评分的差异表达基因并进行 GO 及 KEGG 富集分析.采用 CIBERSORT 算法评估免疫细胞富集程度,分析不同 TLS 评分下免疫微环境状态.使用 maftools 计算肿瘤突变负荷(TMB),并分析其与TLS评分的相关性,同时比较免疫检查点基因的表达差异.结果 高评分 TLS 患者的总生存率高于低评分 TLS 患者(P<0.05),Cox 回归分析显示 TLS 评分、年龄和分期是 HNSCC 患者临床预后的独立影响因素(P 均<0.05).差异表达基因主要富集于细胞因子-细胞因子受体相互作用、T 细胞受体信号通路及 B 细胞受体信号通路等肿瘤免疫相关通路.高 TLS 评分与低 TLS 评分相比,多种抗肿瘤免疫细胞富集程度更高(P 均<0.05).TLS 评分与 TMB 呈负相关(P<0.05),TP53、TTN、FAT1和 CDKN2A 等基因在 HNSCC 中突变频率较高,且高评分 TLS 中11 个免疫检查点基因表达水平高于低评分 TLS 组(P 均<0.05).结论 TLS 水平与 HNSCC 患者预后及肿瘤免疫微环境密切相关,TLS 评分可能作为 HNSCC 潜在预后评估指标,并为免疫治疗及靶向治疗策略的制定提供参考.
Objective To investigate the immune characteristics of tertiary lymphoid structure(TLS)in head and neck squamous cell carcinoma(HNSCC),their prognostic value,and their associations with the tumor immune microenvi-ronment and mutational features,so as to provide a reference for the formulation of treatment strategies for HNSCC.Methods Transcriptomic data and clinical information of 522 tumor samples and 44 normal control samples were obtained from The Cancer Genome Atlas(TCGA)database.TLS scores were calculated using single-sample gene set enrichment a-nalysis(ssGSEA),and patients were stratified into the high-score TLS and low-score TLS based on the optimal cut-off val-ue.Survival analysis and Cox regression were performed to assess prognostic significance.Differentially expressed genes were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses.We evaluated the enrichment of immune cells using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algorithm and analyzed the status of the immune microenvironment under different TLS scores.We calculat-ed the tumor mutation burden(TMB)with maftools and analyzed its correlation with TLS scores.Meanwhile,the expression differences of immune checkpoint genes were compared.Results Overall survival was higher in the high-score TLS than in the low-score TLS(P<0.05).TLS score,age,and stage were independent influencing factors for clinical prognosis of HNSCC patients(all P<0.05).Differentially expressed genes were mainly enriched in tumor immunity-related pathways such as cyto-kine-cytokine receptor interaction,T-cell receptor signaling pathway,and B-cell receptor signaling pathway.The high-score TLS showed higher infiltration levels of multiple antitumor immune cells(all P<0.05).TLS score was negatively correlated with TMB(P<0.05).TP53,TTN,FAT1,and CDKN2A had high mutation frequencies.In addition,the expression levels of 11 immune checkpoint genes in the high-score TLS group were higher than those in the lows-core TLS group(all P<0.05).Conclusions TLS is closely associated with prognosis and the tumor immune microenvironment in HNSCC.TLS score may serve as a potential prognostic biomarker and provide insights for immunotherapy and targeted therapy.
王浩然;张梦琪;张宁;张东升;周晓清;徐乐
山东第一医科大学附属省立医院口腔科,山东 济南 250021||山东第一医科大学口腔医学院,山东 济南 250117山东第一医科大学口腔医学院,山东 济南 250117||济宁市第一人民医院口腔科,山东 济宁 272011山东第一医科大学口腔医学院,山东 济南 250117||济宁市第一人民医院口腔科,山东 济宁 272011山东第一医科大学附属省立医院口腔科,山东 济南 250021||山东第一医科大学口腔医学院,山东 济南 250117山东第一医科大学口腔医学院,山东 济南 250117||济宁市第一人民医院口腔科,山东 济宁 272011山东第一医科大学附属省立医院口腔科,山东 济南 250021||山东第一医科大学口腔医学院,山东 济南 250117
医药卫生
三级淋巴结构头颈部鳞状细胞癌生物标志物免疫浸润预后靶向治疗
tertiary lymphoid structurehead and neck squamous cell carcinomabiomarkersimmune infiltrationprognosistargeted therapy
《山东医药》 2026 (4)
16-20,5
山东省自然科学基金青年项目(ZR2022QH395).
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