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PNPO在泛癌中的预后意义及致癌作用

Prognostic Implication and Oncogenic Role of PNPO in Pan-Cancer.

作者信息

Zhang Lingyun, Li Xin, Zhang Jinguo, Xu Guoxiong

机构信息

Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.

Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Front Cell Dev Biol. 2022 Jan 21;9:763674. doi: 10.3389/fcell.2021.763674. eCollection 2021.

Abstract

Pyridoxine 5'-phosphate oxidase (PNPO) is a key enzyme in the metabolism of vitamin B6 and affects the tumorigenesis of ovarian and breast cancers. However, the roles of PNPO in other types of cancer remain unknown. The expression of PNPO was interpreted by The Cancer Genome Atlas (TCGA) database and Genotype Tissue-Expression (GTEX) database. Analysis of PNPO genomic alterations and protein expression in human organic tissues was analyzed by the cBioPortal database and human multiple organ tissue arrays. PNPO with drug sensitivity analysis was performed from the CellMiner database. The correlations between PNPO expression and survival outcomes, clinical features, DNA mismatch repair system (MMR), microsatellite instability (MSI), tumor mutation burden (TMB), and immune-associated cell infiltration were analyzed using the TCGA, ESTIMATE algorithm, and TIMER databases. Gene Set Enrichment Analysis (GSEA) was applied to elucidate the biological function of PNPO in pan-cancer. The differential analysis showed that the level of PNPO mRNA expression was upregulated in 21 tumor types compared with normal tissues, which was consistent with its protein expression in most cancer types. The abnormal expression of PNPO could predict the survival outcome of patients with esophageal carcinoma (ESCA), kidney renal clear cell carcinoma (KIRC), prostate adenocarcinoma (PRAD), ovarian serous cystadenocarcinoma (OV), and uveal melanoma (UVM). Furthermore, the most frequent mutation type of PNPO genomic was amplified. Moreover, the aberrant PNPO expression was related to MMR, MSI, TMB, and drug sensitivity in various types of cancer. The expression of PNPO was related to the infiltration levels of various immune-associated cells in pan-cancer by ESTIMATE algorithm and TIMER database mining. Our results suggest that PNPO is a potential molecular biomarker for predicting patient prognosis, drug sensitivity, and immunoreaction in pan-cancer.

摘要

磷酸吡哆醛5'-磷酸氧化酶(PNPO)是维生素B6代谢中的关键酶,影响卵巢癌和乳腺癌的肿瘤发生。然而,PNPO在其他类型癌症中的作用仍不清楚。通过癌症基因组图谱(TCGA)数据库和基因型组织表达(GTEX)数据库解释PNPO的表达。通过cBioPortal数据库和人类多器官组织阵列分析人类有机组织中PNPO的基因组改变和蛋白质表达。从CellMiner数据库进行PNPO与药物敏感性分析。使用TCGA、ESTIMATE算法和TIMER数据库分析PNPO表达与生存结果、临床特征、DNA错配修复系统(MMR)、微卫星不稳定性(MSI)、肿瘤突变负担(TMB)和免疫相关细胞浸润之间的相关性。应用基因集富集分析(GSEA)阐明PNPO在泛癌中的生物学功能。差异分析表明,与正常组织相比,21种肿瘤类型中PNPO mRNA表达水平上调,这与其在大多数癌症类型中的蛋白质表达一致。PNPO的异常表达可以预测食管癌(ESCA)、肾透明细胞癌(KIRC)、前列腺腺癌(PRAD)、卵巢浆液性囊腺癌(OV)和葡萄膜黑色素瘤(UVM)患者的生存结果。此外,PNPO基因组最常见的突变类型是扩增。此外,PNPO的异常表达与各种类型癌症中的MMR、MSI、TMB和药物敏感性相关。通过ESTIMATE算法和TIMER数据库挖掘,PNPO的表达与泛癌中各种免疫相关细胞的浸润水平相关。我们的结果表明,PNPO是预测泛癌患者预后、药物敏感性和免疫反应的潜在分子生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09f/8814662/6bdb48361714/fcell-09-763674-g005.jpg

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