棕榈酰蛋白硫酯酶1在低级别胶质瘤组织中的表达及其临床意义

Expression profile of palmitoyl-protein thioesterase in low-grade gliomas and its clinical significance

目的探讨棕榈酰蛋白硫酯酶1(PPT1)在低级别胶质瘤组织中的表达及其临床意义。方法比较癌症基因组图谱(TCGA)和中国脑胶质瘤基因组图谱(CGGA)中PPT1在脑胶质瘤组织中的表达水平。根据其在肿瘤组织中表达的中位数,将患者分为高低表达组,通过Kaplan-Meier生存分析比较不同病理分级下两组总生存期是否存在差异。收集2017年11月至2020年11月于武汉大学人民医院神经外Ⅲ科行手术治疗的75例患者的胶质瘤组织标本进行免疫组织化学染色验证并分析其与胶质瘤患者预后的关系。组间比较采用方差检验和t检验,生存分析组间比较采用Log-rank检验。最后进行富集分析以探讨PPT1相关的分子信号通路。结果TCGA数据库中低级别胶质瘤PPT1表达量的平均每千碱基对百万转录(TPM)值为120.98±21.35,高级别胶质瘤平均TPM值为174.61±34.28,均高于正常组,差异有统计学意义(t=2.279,2.586,P<0.05)。CGGA数据库中Ⅱ、Ⅲ、Ⅳ级胶质瘤PPT1表达量的平均TPM值分别为82.54±22.26、91.39±27.93和98.40±28.06。在Ⅲ级与Ⅳ级样本中的表达量均高于Ⅱ级样本(t=2.381、4.737,P<0.05),差异有统计学意义。生存分析提示PPT1高表达组和低表达组间总生存期差异均有统计学意义,高表达组与较差的预后明显相关(χ^(2)=34.660,P<0.01)。临床标本免疫组织化学染色显示,Ⅱ~Ⅳ级胶质瘤中均可发现PPT1蛋白的表达,平均吸光度(MOD)值分别为0.643±0.446、0.968±0.479和1.267±0.626。Ⅲ级和Ⅳ级样本中的表达量均高于Ⅱ级样本(t=2.454,3.960,P<0.05)。临床样本PPT1高表达组和低表达组间总生存期差异有统计学意义,高表达组与较差的预后明显相关(χ^(2)=10.200,P<0.01)。PPT1高表达的肿瘤样本最显著富集的通路包括蛋白质降解特征通路,尤其是溶酶体相关基因集。结论PPT1主要与溶酶体相关通路有关,其高表达与患者预后不良明显相关。

Objective To investigate the expression and its clinical characteristics of palmitoyl-protein thioesterase(PPT1)in low-grade gliomas.Methods The expression level of PPT1 in glioma was compared between The Cancer Genome Atlas(TCGA)and Chinese Glioma Genome Atlas(CGGA).Patients were divided into high-and low-expression group according to the median expression in tumor tissue,and Kaplan-Meier survival analysis was performed to compare the difference in overall survival between the two groups under different pathological grades.Clinical samples were collected from 75 patients treated with surgical processes from November 2017 to November 2020 in Department Ⅲ of Neurosurgery,Renmin Hospital,Wuhan University.Immunohistochemical staining was carried to verify and analyze the relationship between the expression of PPT1 and the prognosis of patients with gliomas.Variance test and t-test were used for comparison of expression levels between groups.Log-rank test was used for comparison of survival analysis between groups.Finally,enrichment analysis was carried out to explore PPT1-related molecular signaling pathways.Results In TCGA database,the mean Transcripts Perkilobase Million(TPM)value of PPT1 expression in low-grade gliomas was 120.98±21.35,and that in high-grade gliomas was 174.61±34.28,both of which were significantly higher than those in normal brain tissue samples(t=2.279,2.586,P<0.05).The PPT1 expression in glioma samples of grade Ⅱ,Ⅲ,Ⅳ from CGGA database was 82.54±22.26,91.39±27.93 and 98.40±28.06,respectively.The expression of PPT1 in glioma samples of grade Ⅲ and Ⅳ was significantly increased(t=2.381,4.737,P<0.05).Survival analysis showed that the difference in overall survival between the high-and low-expression groups was statistically significant,and the high-expression of PPT1 was significantly associated with poor prognosis(χ^(2)=34.660,P<0.01).The immunohistochemical staining of clinical specimens showed that PPT1 protein expression could be detectable in all gliomas of grade Ⅱ-Ⅳ.The average of the mean optical density(MOD)in gliomas of grade Ⅱ-Ⅳ was 0.643±0.446,0.968±0.479 and 1.267±0.626,respectively.The expression of PPT1 in grade Ⅲ and Ⅳ samples was significantly increased(t=2.454,3.960,P<0.05).There was significant difference in the overall survival between the high-and low-expression group,and the high-expression of PPT1 was significantly associated with poor prognosis(χ^(2)=10.200,P<0.05).The most significantly enriched pathways in tumor samples with high PPT1 expression included protein degradation characteristic pathways,especially lysosomal related gene sets.Conclusion PPT1 is mainly related to lysosomal-related pathways,and its high expression is associated with poor prognosis of patients.