Department of Emergency, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People's Republic of China.
Department of Pediatrics, Futian Women and Children Health Institute, Shenzhen, People's Republic of China.
Cancer Med. 2020 Aug;9(16):5940-5947. doi: 10.1002/cam4.3251. Epub 2020 Jun 24.
Uridine phosphorylase 1 (UPP1) has been reported as an oncogene in several malignancies. In glioma, the role of UPP1 remains unclear. This study was performed to explore its role in glioma at transcriptional level. Totally, 998 glioma patients with clinical data were enrolled, including 301 mRNA microarray data from Chinese Glioma Genome Atlas (CGGA) dataset and 697 RNAseq data from The Cancer Genome Atlas (TCGA) dataset. Statistical analysis was performed with R language. UPP1 expression level was positively correlated with WHO grade of glioma. UPP1 was significantly upregulated in mesenchymal subtype and could serve as a potential biomarker for this subtype. Based on most correlated genes of UPP1, Gene ontology analysis revealed that UPP1 was profoundly associated with immune and inflammatory response. Gene Sets Variation Analysis was further performed and showed that UPP1 was particularly correlated with MHC-II and LCK, which were mainly associated with activities of antigen-presenting cells and T cells. Moreover, UPP1 was found to be synergistic with various immune checkpoint members, especially with PD1 pathway and B7-H3. Finally, Kaplan-Meier curves revealed that higher UPP1 indicated significantly shorter survival for glioma patients. Taken together, UPP1 played an oncogenic role in glioma via suppressing tumor-related immune response.
尿苷磷酸化酶 1（UPP1）已被报道为多种恶性肿瘤中的癌基因。在神经胶质瘤中，UPP1 的作用尚不清楚。本研究旨在从转录水平探讨其在神经胶质瘤中的作用。共纳入 998 例有临床资料的神经胶质瘤患者，包括来自中国神经胶质瘤基因组图谱（CGGA）数据集的 301 例 mRNA 微阵列数据和来自癌症基因组图谱（TCGA）数据集的 697 例 RNAseq 数据。使用 R 语言进行统计分析。UPP1 的表达水平与神经胶质瘤的 WHO 分级呈正相关。UPP1 在间充质亚型中显著上调，可作为该亚型的潜在生物标志物。基于与 UPP1 最相关的基因，基因本体分析显示 UPP1 与免疫和炎症反应密切相关。进一步进行基因集变异分析表明，UPP1 与 MHC-II 和 LCK 特别相关，这两者主要与抗原呈递细胞和 T 细胞的活性相关。此外，发现 UPP1 与各种免疫检查点成员协同作用，特别是与 PD1 通路和 B7-H3。最后，Kaplan-Meier 曲线显示 UPP1 水平较高的神经胶质瘤患者的生存时间明显缩短。综上所述，UPP1 通过抑制肿瘤相关免疫反应在神经胶质瘤中发挥致癌作用。
