系统的全癌分析揭示了WDR1在肾癌和胃癌中具有不同影响的上下文依赖性预后和免疫作用

摘要(中文译文)

WD重复结构域1（WDR1）是肌动蛋白细胞骨架动力学的关键调节因子，与肿瘤进展有关。然而，其泛癌特征和免疫学相关性仍不清楚。在这项研究中，我们进行了一项综合的全癌分析，以评估WDR1的表达模式、预后价值、分子特征和免疫相关性。我们使用癌症基因组图谱（TCGA）、基因型组织表达（GTEx）和基因表达综合（GEO）的综合数据集，系统分析了癌症中的WDR1。通过整合R软件和在线生物信息学平台（如UALCAN、HPA、GEPIA2、cBioPortal和TIMER2.0），我们从表达、预后和诊断价值、表观遗传调控、遗传变异和免疫细胞浸润等方面对WDR1进行了表征。进一步进行了功能富集和药物敏感性分析，并进行了体外实验进行验证。WDR1在不同癌症中表现出异质性表达，并显示出肿瘤类型依赖的预后意义。此外，WDR1显示出不同的DNA甲基化模式，并与多种RNA甲基化相关调节因子呈正相关。值得注意的是，WDR1的表达与肿瘤免疫微环境特征密切相关，包括髓系和基质细胞浸润的增加以及与免疫检查点分子和免疫相关基因的广泛相关性。功能分析表明，WDR1相关基因主要参与肌动蛋白细胞骨架的组织。药物敏感性分析显示，WDR1表达与对多种治疗药物的不同反应有关。重要的是，实验验证表明，WDR1发挥了上下文依赖性生物效应，抑制癌症肾细胞的增殖、迁移和侵袭，同时促进癌症胃癌细胞的这些表型。我们的研究结果表明，WDR1以上下文依赖的方式与肿瘤进展和免疫微环境重塑相关，可能是癌症进一步研究的潜在生物标志物。

Abstract

WD-repeat domain 1 (WDR1), a key regulator of actin cytoskeleton dynamics, has been implicated in tumor progression. However, its pan-cancer characteristics and immunological relevance remain unclear. In this study, we performed an integrative pan-cancer analysis to evaluate the expression patterns, prognostic value, molecular features, and immune associations of WDR1. We systematically analyzed WDR1 across cancers using integrated datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO). By integrating R software and online bioinformatics platforms (e.g., UALCAN, HPA, GEPIA2, cBioPortal, and TIMER2.0), we characterized WDR1 in terms of expression, prognostic and diagnostic value, epigenetic regulation, genetic variation, and immune cell infiltration. Functional enrichment and drug sensitivity analyses were further conducted, and experiments were performed for validation. WDR1 exhibited heterogeneous expression across cancers and showed tumor-type-dependent prognostic significance. In addition, WDR1 displayed differential DNA methylation patterns and was positively correlated with multiple RNA methylation-related regulators. Notably, WDR1 expression was closely associated with tumor immune microenvironment features, including increased infiltration of myeloid and stromal cells and broad correlations with immune checkpoint molecules and immune-related genes. Functional analyses indicated that WDR1-related genes were primarily involved in actin cytoskeleton organization. Drug sensitivity analysis revealed that WDR1 expression was associated with differential responses to multiple therapeutic agents. Importantly, experimental validation demonstrated that WDR1 exerted context-dependent biological effects, suppressing proliferation, migration, and invasion in renal cancer cells while promoting these phenotypes in gastric cancer cells. Our findings demonstrated that WDR1 was associated with tumor progression and immune microenvironment remodeling in a context-dependent manner and may represent a potential biomarker for further investigation in cancer.

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