摘要
目的 分析组织蛋白酶L(CTSL)基因表达与头颈部鳞状细胞癌(HNSCC)预后及免疫浸润的关系.方法 基于癌症和肿瘤基因组图谱(TCGA)数据库和基因表达综合数据库(GEO)中的GSE41613、GSE65858、GSE27020 和GSE30784 数据集,分析CTSL基因在HNSCC组织和正常组织中的表达差异.根据最佳截断值将HNSCC患者分为CTSL基因高表达和低表达组.采用单因素和多因素Cox回归分析,确定CTSL基因表达对HNSCC的预后预测价值.利用免疫亚型、ESTIMATE法、CIBERSORT法和基因集变异分析(GSVA)法分析CTSL基因高表达和低表达组HNSCC的免疫浸润差异.利用TCGA数据库和GSE65858 数据集分析不同人乳头状瘤病毒(HPV)感染状态下CTSL基因对HNSCC预后和免疫浸润的影响.利用TCGA数据库进行泛癌分析.结果 在TCGA数据库和GSE30784数据集中,CTSL基因在HNSCC组织中的相对表达量分别为 6.90±1.07 和 9.54±0.87,均高于正常组织(分别为 5.46±1.20 和 7.96±0.59,均 P＜0.05).在 TCGA 数据库和GSE65858 数据集中,CTSL基因在HPV阴性HNSCC组织中的相对表达量分别为7.16±0.94 和 8.66±0.54,均明显高于HPV阳性HNSCC组织(分别为 6.10±1.18 和8.41±0.51,均P＜0.05).在TCGA数据库和GSE41613、GSE65858、GSE27020 数据集中,单因素Cox回归分析显示,与CTSL基因低表达组比较,CTSL基因高表达组的 HR值分别为 1.64(95%CI:1.24～2.17,TCGA 数据库总生存时间)、1.62(95%CI:1.15～2.28,TCGA数据库无进展生存时间)、2.42(95%CI:1.31～4.46,GSE41613数据集总生存时间)、2.22(95%CI:1.29～3.81,GSE65858数据集总生存时间)和 2.66(95%CI:1.53～4.63,GSE27020 数据集无病生存时间);多因素Cox回归分析显示,与CTSL基因低表达组比较,CTSL基因高表达组的HR值分别为1.55(95%CI:1.17～2.06,TCGA数据库总生存时间)、1.56(95%CI:1.09～2.21,TCGA数据库无进展生存时间)、2.06(95%CI:1.10～3.88,GSE41613 数据集总生存时间)、2.33(95%CI:1.35～4.02,GSE65858 数据集总生存时间)和 2.64(95%CI:1.48～4.72,GSE27020 数据集无病生存时间).CTSL 基因高表达与HNSCC的不良预后有关(均P<0.05).单因素和多因素荟萃分析显示,CTSL基因高表达组的HR值分别为 1.93(95%CI:1.56～2.39)和 1.84(95%CI:1.48～2.29).在TCGA数据库中,免疫浸润分析结果显示,CTSL基因高表达组HNSCC的免疫浸润水平较高,具有更有利的免疫激活表型.在GSE65858 数据集中,不同CTSL基因和HPV感染状态与HNSCC的预后和免疫浸润相关,与HPV阴性且CTSL高表达组比较,HPV阳性且CTSL低表达组患者的预后相对较好(χ2=15.39,P=0.002).在TCGA数据库中,CTSL基因的表达与多形性胶质细胞瘤、肾透明细胞癌、低级别脑胶质瘤、肝细胞癌、肺腺癌、肺鳞癌和葡萄膜黑色素瘤的总生存时间有关(均P＜0.05);与多形性胶质细胞瘤、肾透明细胞癌、低级别脑胶质瘤、肺腺癌、肺鳞癌和前列腺癌的无进展生存时间有关,CTSL基因表达越高,患者预后越差(均P＜0.05).结论 CTSL基因的表达水平与HNSCC患者的预后和免疫浸润密切相关,并且与不同HPV感染状态具有相互作用.
Abstract
Objective To analyze the relationship between cathepsin L(CTSL)gene expression and prognosis and immune infiltration in head and neck squamous cell carcinoma(HNSCC).Methods Based on data from The Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO)datasets,including GSE41613,GSE65858,GSE27020,and GSE30784,we analyzed the expression differences of the CTSL gene in HNSCC tissues compared to normal tissues.Patients were divided into high and low CTSL expression groups according to the optimal cut-off point.Cox regression analysis was employed to determine the comprehensive prognostic value of CTSL.The differences in immune infiltration between the high and low CTSL expression groups were analyzed using immunophenotyping,Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data(ESTIMATE),Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts(CIBERSORT),and gene set variation analysis(GSVA).In addition,the TCGA database and GSE65858 dataset were used to analyze the effects of CTSL on the prognosis and immune infiltration of HNSCC in different HPV infection states.Finally,pan-cancer analysis was performed using the TCGA database.Results In the TCGA database and the GSE30784 dataset,the relative expression levels of the CTSL gene in HNSCC tissues were 6.90±1.07 and 9.54±0.87,respectively,both of which were higher than those in normal tissues(5.46±1.20 and 7.96±0.59,respectively;all P<0.05).In the TCGA database and the GSE65858 dataset,the expression levels of the CTSL gene in HPV-negative HNSCC tissues were 7.16±0.94 and 8.66±0.54,respectively,which were significantly higher than those in HPV-positive HNSCC tissues(6.10±1.18 and 8.41±0.51,respectively;all P<0.05).In the TCGA database(overall survival and progression-free survival)and the GSE41613(overall survival),GSE65858(overall survival),and GSE27020(disease-free survival)datasets,univariate Cox regression analysis showed that compared to the low expression group of the CTSL gene,the high expression group had hazard ratios(HR)of 1.64(95%CI:1.24～2.17),1.62(95%CI:1.15～2.28),2.42(95%CI:1.31～4.46),2.22(95%CI:1.29～3.81),and 2.66(95%CI:1.53～4.63).Multivariate Cox regression analysis indicated that compared to the low expression group,the high expression group had HRs of 1.55(95%CI:1.17～2.06),1.56(95%CI:1.09～2.21),2.06(95%CI:1.10～3.88),2.33(95%CI:1.35～4.02),and 2.64(95%CI:1.48～4.72).The HR from the univariate and multivariate meta-analyses were 1.93(95%CI:1.56～2.39)and 1.84(95%CI:1.48～2.29),respectively.Immune infiltration analysis indicated that the high CTSL expression group had higher immune infiltration and a more favorable immune-activated phenotype in the TCGA database.In the GSE65858 dataset,the different expression levels of the CTSL gene and HPV infection status were associated with the prognosis and immune infiltration of HNSCC.Compared to the HPV-negative and high CTSL expression group,the HPV-positive and low CTSL expression group had a relatively better prognosis(χ2=15.39,P=0.002).In the TCGA database,CTSL gene expression was associated with overall survival in patients with glioblastoma,clear cell renal carcinoma,low-grade glioma,hepatocellular carcinoma,lung adenocarcinoma,lung squamous cell carcinoma,and uveal melanoma(all P<0.05).Additionally,higher CTSL gene expression was linked to worse prognosis in terms of progression-free survival in glioblastoma,clear cell renal carcinoma,low-grade glioma,lung adenocarcinoma,lung squamous cell carcinoma,and prostate cancer(all P<0.05).Conclusion The expression level of the CTSL gene is closely related to the prognosis and immune cell infiltration of HNSCC patients,and interacts with different HPV infection states.
NETL
NSTL
万方数据