肾透明细胞癌PTTG1基因与免疫细胞浸润的相关性

Correlation of PTTG1 with tumour immune infiltration in kidney renal clear cell carcinoma

目的 阐明垂体瘤转化基因(PTTG1)与肾透明细胞癌(KIRC)预后及肿瘤免疫细胞浸润的关系。方法 用TCGA数据库获取KIRC样本的相关数据;分析PTTG1在KIRC中的表达水平及临床分期和预后的相关性;用qPCR检测KIRC细胞和肾小管上皮细胞中PTTG1的表达水平;在The Human Protein Atlas数据库中分析PTTG1的蛋白表达水平;分析PTTG1基因和肿瘤免疫浸润的关系;用GSEA进行通路富集分析。结果 KIRC组织中PTTG1 mRNA的转录水平较正常组织显著升高(P<0.01),具有较高的诊断价值。PTTG1与TNM分期和病理分期均存在相关性。PTTG1高表达组的患者总生存期(OS)、疾病特异生存率(DSS)和无进展间隔期(PFS)均显著短于低表达组(P<0.01),PTTG1高表达是影响患者预后的独立危险因素。PTTG1基因表达与Th2、Treg和Th1细胞的浸润程度呈显著正相关(P<0.01)。GSEA结果证实PTTG1主要参与细胞周期及免疫相关的信号通路。结论 PTTG1有望成为KIRC潜在的诊断和预后生物标志物及免疫治疗靶点。

Objective To explore the correlation of the expression of PTTG1 with clinical prognosis and tumor immune infiltration in kidney renal clear cell carcinoma(KIRC).Methods The expression of PTTG1 in KIRC and the correlation with clinical stages, clinical prognosis were analyzed based on TCGA database. qPCR was performed to measure PTTG1 expression in renal cancer cell lines and kidney proximal tubular epithelial cell line. The Human Protein Atlas was used to analyze the protein expression level of PTTG1. The relationship between PTTG1 gene and tumor immune infiltration was analyzed. GSEA analysis was performed to explore the pathway enrichment.Results The transcription level of PTTG1 in KIRC tissues was significantly higher than that in normal tissues(P<0.01), which has high diagnostic value. There was a significant association between high PTTG1 expression and TNM stage. Patients with higher PTTG1 expression had a significantly shorter overall survival(OS), disease-specific survival rate(DSS), and progression-free interval(PFS) than those with lower PTTG1 expression(P<0.01). High PTTG1 expression was an independent unfavourable prognostic factor for KIRC patients. In addition, a significant positive correlation was found between PTTG1 expression and Th2 cells, Treg, Th1 cells infiltration(P<0.01). GSEA results showed that PTTG1 mainly involved in cell cycle and immune-related signaling pathway.Conclusion PTTG1 could serve as a potential diagnostic and prognostic biomarker for KIRC and a immuno-oncology therapeutic target.