Zhang Chunyu, Wang Long, Liu Haitao, Deng Gang, Xu Pengfei, Tan Yinqiu, Xu Yang, Liu Baohui, Chen Qianxue, Tian Daofeng
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, P.R.C.
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314001, Zhejiang Province, P.R.C.
J Cancer. 2021 Mar 15;12(10):2912-2920. doi: 10.7150/jca.51643. eCollection 2021.
ADPRH is a modulator of CD8+ T cell functions, and dysregulation of ADPRH has been identified to involve in carcinogenesis of cancers. However, the association of ADPRH with low grade glioma (LGG) remains unclear. The expression of ADPRH in LGG was first analyzed in GLIOVIS and GEPIA databases and then validated by real-time PCR (rt-PCR), immunochemistry and human protein atlas (HPA). Univariate and multivariate Cox analysis and Kaplan-Meier plots were designed to assess the prognostic value of ADPRH in LGG. The correlation of ADPRH and immune infiltration was evaluated by data in TIMER and ESTIMATE databases. Gene set enrichment analysis was conducted to detect biological processes associated with ADPRH. ADPRH was significantly upregulated in LGG in comparison to non-tumor brain samples in transcriptomic and proteomic levels. The high ADPRH expression indicated unfavorable overall survival (OS) and progression-free survival (PFS) in patients with LGG using Kaplan-Meier plots. And multivariate Cox analysis demonstrated the expression level of ADPRH was an independent prognosis-predicting index for OS and PFS of LGG patients in all cohorts separately. Gene Set Enrichment Analysis (GSEA) indicated that high expression of ADPRH was involved in the upregulation of P53 signaling pathway, KRAS signaling pathway, IL6/JAK-STAT3 signaling and TNF-beta signaling pathways. By TIMER and ESTIMATE databases, we identified ADPRH expression had strong correlation with tumor immune infiltrating cells (TIICs). In summary, our findings demonstrated that ADPRH might be a potential prognostic biomarker and correlated with TIICs in LGG.
ADPRH是CD8 + T细胞功能的调节剂，并且已确定ADPRH的失调与癌症的致癌作用有关。然而，ADPRH与低级别胶质瘤（LGG）的关联仍不清楚。首先在GLIOVIS和GEPIA数据库中分析ADPRH在LGG中的表达，然后通过实时PCR（rt-PCR）、免疫化学和人类蛋白质图谱（HPA）进行验证。设计单因素和多因素Cox分析以及Kaplan-Meier图来评估ADPRH在LGG中的预后价值。通过TIMER和ESTIMATE数据库中的数据评估ADPRH与免疫浸润的相关性。进行基因集富集分析以检测与ADPRH相关的生物学过程。与非肿瘤脑样本相比，LGG中ADPRH在转录组和蛋白质组水平上显著上调。使用Kaplan-Meier图显示，ADPRH高表达表明LGG患者的总生存期（OS）和无进展生存期（PFS）不佳。多因素Cox分析表明，ADPRH的表达水平分别是所有队列中LGG患者OS和PFS的独立预后预测指标。基因集富集分析（GSEA）表明，ADPRH的高表达参与了P53信号通路、KRAS信号通路、IL6/JAK-STAT3信号通路和TNF-β信号通路的上调。通过TIMER和ESTIMATE数据库，我们发现ADPRH表达与肿瘤免疫浸润细胞（TIICs）密切相关。总之，我们的研究结果表明，ADPRH可能是一种潜在的预后生物标志物，并且与LGG中的TIICs相关。
