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系统分析 WDR62 在人类肿瘤中的致癌作用。

Systematic Analysis of the Oncogenic Role of WDR62 in Human Tumors.

机构信息

Jinming Yu Academician Workstation of Oncology, Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang 261031, China.

Department of Radiotherapy, Affiliated Hospital of Weifang Medical University, Weifang 261031, China.

出版信息

Dis Markers. 2021 Jul 1;2021:9940274. doi: 10.1155/2021/9940274. eCollection 2021.

Abstract

BACKGROUND

Emerging studies support the oncogenic role of WD repeat domain 62 (WDR62) in few tumors, while no pan-cancer analysis is available. In this study, we analyzed systematically the oncogenic role of WDR62 across a series of human tumors based on bioinformatic data mining.

METHODS

The expression level of WDR62 was analyzed via GEPIA2, TIMER, UALCAN, and StarBase databases. The prognostic role was analyzed via GEPIA2, TIMER, UALCAN, StarBase, TISIDB, TCGA portal, Kaplan-Meier Plotter, and PrognoScan databases. Then, we explored the causes for WDR62 abnormal expression via TCGA portal and UALCAN databases. Subsequently, the STRING and GeneMANIA databases were used to find the interactive networks for WDR62. Furthermore, we analyzed the correlation between WDR62 expression and immune features via TIMER and TISIDB databases.

RESULTS

We found that WDR62 was significantly upregulated in most of the tumors and correlated with poor prognosis mainly in 6 candidate tumors-BLCA, BRCA, KIRC, KIRP, LIHC, and LUAD. Abnormal WDR62 expression may be probably attributed to TP53 mutation and promoter DNA methylation. Relative network analysis demonstrated that WDR62 was mainly involved in MAPK and toll-like receptor signaling pathway. WDR62 expression was associated with various immune cell infiltrations, especially cancer-associated fibroblasts (CAF) and T cell regulatory (Treg) cells, and was markedly correlated with poor prognosis. Moreover, WDR62 expression was closely associated with the expression of some immunomodulators such as PD-L1 and has a significant prognostic value.

CONCLUSIONS

Our study revealed that WDR62 could serve as a diagnostic and prognostic biomarker for several cancers. Importantly, WDR62 was closely associated with various immune cell infiltration, and to a certain extent, it can predict the effect of immunotherapy in particular PD1/PD-L1 inhibitors. Our pan-cancer study provided useful information on the oncogenic role of WDR62, contributing to further exploring the underlying mechanisms.

摘要

背景

新兴研究支持 WD 重复结构域 62(WDR62)在少数肿瘤中的致癌作用,而尚无泛癌分析。在这项研究中,我们基于生物信息学数据挖掘,系统分析了 WDR62 在一系列人类肿瘤中的致癌作用。

方法

通过 GEPIA2、TIMER、UALCAN 和 StarBase 数据库分析 WDR62 的表达水平。通过 GEPIA2、TIMER、UALCAN、StarBase、TISIDB、TCGA 门户、Kaplan-Meier Plotter 和 PrognoScan 数据库分析预后作用。然后,我们通过 TCGA 门户和 UALCAN 数据库探索 WDR62 异常表达的原因。随后,使用 STRING 和 GeneMANIA 数据库寻找 WDR62 的相互作用网络。此外,我们通过 TIMER 和 TISIDB 数据库分析 WDR62 表达与免疫特征之间的相关性。

结果

我们发现,WDR62 在大多数肿瘤中显著上调,在 6 种候选肿瘤-BLCA、BRCA、KIRC、KIRP、LIHC 和 LUAD 中主要与预后不良相关。WDR62 的异常表达可能归因于 TP53 突变和启动子 DNA 甲基化。相对网络分析表明,WDR62 主要参与 MAPK 和 Toll 样受体信号通路。WDR62 的表达与各种免疫细胞浸润有关,特别是癌症相关成纤维细胞(CAF)和 T 细胞调节(Treg)细胞,并且与预后不良显著相关。此外,WDR62 的表达与一些免疫调节剂如 PD-L1 的表达密切相关,具有显著的预后价值。

结论

我们的研究表明,WDR62 可以作为几种癌症的诊断和预后生物标志物。重要的是,WDR62 与各种免疫细胞浸润密切相关,在一定程度上可以预测免疫治疗特别是 PD1/PD-L1 抑制剂的效果。我们的泛癌研究提供了关于 WDR62 致癌作用的有用信息,有助于进一步探索潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc2/8272457/7780233fff20/DM2021-9940274.001.jpg

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