目的

通过癌症基因组图谱（TCGA）和基因表达量关联数据库（GTEx）探究组织型纤溶酶原激活物（PLAT）基因在胶质瘤中的表达及预后，为胶质瘤诊断及治疗提供靶点。

方法

利用TCGA 和GTEx数据库分析PLAT 在胶质瘤组织和正常组织间的表达差异，以及PLAT 表达水平与临床病理参数[如性别、年龄、异柠檬酸脱氢酶（IDH）启动子突变状态和1p/19q 是否共缺失等] 之间的关系。采用Kaplan-Meier 生存分析评估PLAT 对胶质瘤患者预后的影响，采用基因本体及京都基因和基因组百科全书数据库富集分析筛选分子功能和信号通路，使用CIBERSORT 算法分析免疫浸润水平与胶质瘤中PLAT 表达水平的相关性，进行单细胞转录组测序和空间转录组测序。

结果

PLAT 在胶质瘤中高表达（P=0.002，95%CI：0.06～0.30），并且在年龄＞60 岁（P＜0.05，95%CI：1.26～1.88）、IDH 野生型（P＜0.05，95%CI：-2.79～-2.46）和1p/19q 未共缺失型（P＜0.05，95%CI：-1.41～-0.87）患者中也表现出高表达。PLAT 上调与胶质瘤患者更差的总生存期（OS）相关（HR=6.48，95%CI：4.81～8.74，P＜0.001），并具有较高的诊断价值[曲线下面积（AUC）=0.931] ，基于PLAT 表达水平预测的胶质瘤患者1、3和5年生存率AUC值均高于0.7。信号通路分析显示，PLAT显著相关的通路有神经活性配体-受体相互作用、细胞因子-细胞因子受体相互作用、IL-17 信号通路。PLAT 的表达与肿瘤免疫微环境中巨噬细胞M0、滤泡辅助性T 细胞的浸润水平呈正相关，与单核细胞的浸润水平呈负相关。单细胞转录组分析显示，PLAT 在间充质样细胞和少突胶质细胞祖细胞中显著表达。空间转录组分析显示，PLAT 主要分布在靠近肿瘤细胞的位置，与前述定位结果高度一致，且PLAT 表达量与肿瘤细胞含量呈正相关。

结论

PLAT 的表达水平在胶质瘤中显著升高，并与更差的生存率相关，是诊断、治疗及预后的潜在肿瘤标志物。

Objective

To investigate the expression and prognosis of plasminogen activator（PLAT） gene in glioma through The Cancer Genome Atlas （TCGA） and Genotype-Tissue Expression（GTEx），and to provide a target for the diagnosis and treatment ofglioma.

Methods

The TCGA and GTEx databases were used to analyze the expression difference of PLAT between gliomatissues and normal tissues. The relationship between PLAT expression level and clinicopathological parameters such as gender，age，isocitrate dehydrogenase （IDH） promoter mutation status and 1p/19q co-deletion； Kaplan-Meier survival analysis of the prognostic value of PLAT in glioma；Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to screen molecular functions and signaling pathways. CIBERSORT algorithm was used to analyze the correlation between immune infiltration level and PLAT expression level in glioma. Single-cell transcriptome sequencing and spatial transcriptome sequencing were performed.

Results

PLAT was highly expressed in glioma （P=0.002，95%CI：0.06-0.30），and was also expressed in 1p/19q non-codeletion[P＜0.05，95%CI：-2.79-（2.46）] ，IDH wild-type[P＜0.05，95%CI：-2.79-（2.46）] ，patients aged ＞60 years （P＜0.05，95%CI：1.26-1.88），yet was no statistically significant difference in expression between males and females （P＞0.05）. Upregulation of PLAT gene was associated with worse overall survival （OS）in glioma patients（HR=6.48，95%CI：4.81-8.74，P＜0.001）and had a high diagnostic value [area under the curve（AUC）=0.931].The AUC values for predicting of the 1-，3-，and 5-year survival rates of glioma patients based on PLAT expression levels were higher than 0.7.Signal pathway analysis showed that PLAT gene included neuroactive ligand-receptor interaction，cytokine-cytokine receptor interaction and IL-17 signaling pathway. In addition，PLAT expression was positively correlated with the infiltration level of macrophage M0 and follicular helper T cells in the tumor immune microenvironment，but negatively correlated with the infiltration level of monocytes. Single - cell transcriptome analysis further indicated that the PLAT gene was significantly expressed in mesenchymallike cells and oligodendrocyte progenitor cells. The spatial transcriptome results also showed that PLAT was mainly distributed near the tumor cells，which was highly consistent with the above mapping results，and the expression level of PLAT was significantly positively correlated with of tumor cells.

Conclusion

The expression level of PLAT is significantly increased in glioma and is associated with worse survival.PLAT is a potential tumor marker for diagnosis，treatment and prognosis.