Zhao Mingyu, Chen Shanshuang
Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Translational Medicine On Ear and Nose Diseases, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Oncol. 2025 Jan 13;14:1527226. doi: 10.3389/fonc.2024.1527226. eCollection 2024.
The Wnt/planar cell polarity (PCP) signaling pathway is pivotal in regulating various biological processes such as early embryonic development, neural crest cell migration, and cancer invasion. Despite advances in understanding the role of Wnt/PCP pathway dysregulation in tumorigenesis, numerous unanswered questions remain. Our study focused on VANGL2, a core PCP gene, to elucidate its potential mechanistic involvement in cancer development.
A systematic analysis was conducted to assess VANGL2 expression patterns at both transcriptional and proteomic levels. Functional enrichment analysis was performed to investigate the biological pathways associated with VANGL2 in glioma. experiments were conducted to assess the impact of VANGL2 on glioma cell behaviors. Furthermore, rigorous methodologies were employed in survival analysis to control for confounding factors.
We identified substantial upregulation of VANGL2 gene in both low-grade glioma (LGG) and glioblastoma (GBM). Functional enrichment analysis of genes positively associated with VANGL2 in glioma underscored their enrichment in Notch signaling and pathway regulating pluripotency of stem cells. experiments further confirmed that VANGL2 promotes glioma cell migration, invasion, proliferation, and tumor sphere formation. We identified a significant correlation between increased VANGL2 expression and IDH mutation in glioma patients. Elevated VANGL2 expression was identified as a predictor of poor prognosis in glioma.
Our analysis of the expression and prognostic features of the core PCP gene VANGL2 underscored its critical roles in glioma oncogenesis and progression.
Wnt/平面细胞极性（PCP）信号通路在调节多种生物学过程中起关键作用，如早期胚胎发育、神经嵴细胞迁移和癌症侵袭。尽管在理解Wnt/PCP通路失调在肿瘤发生中的作用方面取得了进展，但仍有许多未解决的问题。我们的研究聚焦于核心PCP基因VANGL2，以阐明其在癌症发展中潜在的机制性作用。
进行了系统分析，以评估VANGL2在转录和蛋白质组水平的表达模式。进行功能富集分析，以研究与VANGL2在胶质瘤中相关的生物学通路。进行实验以评估VANGL2对胶质瘤细胞行为的影响。此外，在生存分析中采用了严格的方法来控制混杂因素。
我们在低级别胶质瘤（LGG）和胶质母细胞瘤（GBM）中均发现VANGL2基因显著上调。对胶质瘤中与VANGL2呈正相关的基因进行功能富集分析，强调了它们在Notch信号通路和调节干细胞多能性的通路中的富集。实验进一步证实，VANGL2促进胶质瘤细胞迁移、侵袭、增殖和肿瘤球形成。我们发现胶质瘤患者中VANGL2表达增加与异柠檬酸脱氢酶（IDH）突变之间存在显著相关性。VANGL2表达升高被确定为胶质瘤预后不良的预测指标。
我们对核心PCP基因VANGL2的表达和预后特征分析强调了其在胶质瘤发生和进展中的关键作用。
