SPP1在头颈部鳞状细胞癌的免疫浸润及临床相关性分析

Immune infiltration of SPP1 in head and neck squamous cell carcinoma and its clinical correlation analysis

探讨分泌型磷蛋白1 (Secreted Phosphoprotein 1,SPP1)在头颈部鳞状细胞癌(Head and neck squamous cell carcinoma, HNSC)中与免疫浸润及临床的相关性,明确SPP1在HNSC预后和个体化治疗中的潜在价值。使用癌症基因组图谱(The Cancer Genome Atlas, TCGA)HNSC数据分析SPP1表达。使用来自TCGA的临床生存数据评估SPP1的临床预后价值。使用R语言的clusterProfiler包进行SPP1相关的富集分析。使用R语言的CIBERSORT函数评估22种肿瘤浸润免疫细胞在HNSC中的浸润情况,分析肿瘤浸润免疫细胞与SPP1表达之间的关联。差异表达分析发现SPP1在HNSC中高表达(P<0.001),临床相关性分析发现SPP1表达与T分期(P=0.001)、临床分期(P=0.013)相关,SPP1高表达患者的总生存期明显短于低表达患者(P=0.020 4)。基因富集分析发现SPP1在HNSC中与免疫学功能及免疫相关通路有关联。肿瘤浸润免疫细胞分析发现在高SPP1表达组中,M2巨噬细胞(P=0.001 1)、未活化树突状细胞(P=0.005 5)、活化肥大细胞(P=0.048 8)浸润比例增加,而活化记忆性CD4+T淋巴细胞(P<0.001)、浆细胞(P=0.026 6)、未活化肥大细胞(P=0.038 6)浸润比例减少。研究表明SPP1在HNSC中充当致癌基因,并与患者的临床结果相关,SPP1在肿瘤免疫微环境中起重要作用,可能成为HNSC中有价值的预后生物标志物及免疫治疗生物靶标。

The correlation between secreted phosphoprotein 1(SPP1) and immune infiltration and the clinical correlation of SPP1 in head and neck squamous cell carcinoma(HNSC) were analyzed, and the potential value of SPP1 in the prognosis and individualized treatment of HNSC was clarified. The HNSC data from The Cancer Genome Atlas(TCGA) was used to analyze SPP1 expression. The clinical survival data from TCGA was used to evaluate the clinical prognostic value of SPP1. The clusterProfiler package of R language was applied for the enrichment analysis related to SPP1. The CIBERSORT function of R language was used to evaluate the infiltration of 22 kinds of tumor infiltrating immune cells in HNSC. Subsequently, the correlation analysis between tumor infiltrating immune cells and SPP1 expression was performed. Differential expression analysis found that SPP1 was highly expressed in HNSC(P<0.001). Clinical correlation analysis found that SPP1 expression was correlated with T stage(P=0.001) and clinical stage(P=0.013). The overall survival of patients with high SPP1 expression was significantly shorter than the patients with low SPP1 expression(P=0.020 4). Gene enrichment analysis found that SPP1 was associated with immunological functions and immune-related pathways in HNSC. Analysis of tumor infiltrating immune cells found that in the high SPP1 expression group, the infiltration proportions of M2 macrophages(P=0.001 1), resting dendritic cells(P=0.005 5), and activated mast cells(P=0.048 8) increased, while the infiltration proportions of actived memory CD4+ T lymphocytes(P<0.001), plasma cells(P=0.026 6), and resting mast cells(P=0.038 6) decreased. The research results indicate that SPP1 acts as an oncogene in HNSC and is related to the clinical outcome of patients. SPP1 may play an important role in the tumor immune microenvironment and may become a valuable prognostic biomarker and immunotherapy target in HNSC.