Background and Objective. Glutamate-rich WD repeat-containing protein 1 (GRWD1), as a novel CDT1-binding protein, plays a critical role in the initial stage of DNA replication. To date, few studies have shown that GRWD1 is a driving factor for lung cancer, bladder cancer, and colorectal cancer. However, no systematic pancancer analysis has been carried out. This study was aimed at exploring its expression signature, prognostic value, immune infiltration pattern, and biological functions using bioinformatics tools. Methods. The expression level of GRWD1 in human cancer tissues was analyzed using the Tumor Immune Evaluation Resource (ver. 2.0, TIMER2), Gene Expression Profiling Interactive Analysis (ver. 2, GEPIA2), and UALCAN databases. The Kaplan-Meier plotter was utilized to analyze the survival data. Spearman’s correlation analysis was used to find out the correlation between the expression level of GRWD1 and predictive biomarkers, such as tumor mutation burden (TMB) and microsatellite instability (MSI). Furthermore, the MEXPRESS website was used to study the potential relationship between DNA methylation level of GRWD1 and pathological staging. We utilized the “immune” module provided on the TIMER2 website to explore the relationship between the expression level of GRWD1 and immune infiltration in all types of cancer in TCGA. Pearson’s correlation analysis was used to investigate the correlation between the expression level of GRWD1 and the expression levels of immune checkpoint-related genes. For protein expression analysis, we used the CPTAC module provided by the UALCAN portal to compare the total protein and phosphorylated protein level of GRWD1 in adjacent normal and tumor tissues. Results. GRWD1 was overexpressed in tissues of most types of cancer, in which the expression levels of GRWD1 in the kidney chromophobe (KICH), kidney renal papillary cell carcinoma (KIRP), and kidney renal clear cell carcinoma (KIRC) tissues showed an opposite trend, and the expression level of GRWD1 was correlated to only the KIRC tumor stage. The results of survival analysis showed that the expression level of GRWD1 was significantly associated with overall survival in six types of cancer and disease-free survival (DFS) in three types of cancer. Importantly, the increased expression level of GRWD1 was strongly correlated with prognosis of KIRC patients. There was a positive relationship between the expression level of GRWD1 and immune cell infiltration in several types of cancer, and the expression level of GRWD1 was also positively correlated with TMB, MSI, and DNA methylation in some types of cancer. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that “ubiquitin mediated proteolysis,” “spliceosome,” and “nucleotide excision repair” were involved in the effect of GRWD1 expression on tumor pathogenesis. Conclusion. This pancancer analysis provided a comprehensive overview of the carcinogenic effects of GRWD1 on a variety of human cancers. The results of bioinformatics analysis indicated GRWD1 as a promising biomarker for detection, prognosis, and therapeutic assessment of diverse types of cancer, and GRWD1 could act as a tumor suppressor in KIRC.

中文翻译：

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富含谷氨酸的WD重复蛋白1的综合分析及其对泛癌的潜在临床意义

背景和目的。富含谷氨酸的 WD 重复蛋白 1 (GRWD1) 作为一种新型的 CDT1 结合蛋白，在 DNA 复制的初始阶段起着至关重要的作用。迄今为止，很少有研究表明GRWD1是肺癌、膀胱癌和结直肠癌的驱动因素。然而，尚未进行系统的泛癌分析。本研究旨在利用生物信息学工具探索其表达特征、预后价值、免疫浸润模式和生物学功能。方法. 使用肿瘤免疫评估资源（2.0 版，TIMER2）、基因表达谱交互分析（2 版，GEPIA2）和 UALCAN 数据库分析人类癌症组织中 GRWD1 的表达水平。Kaplan-Meier 绘图仪用于分析生存数据。Spearman相关分析用于找出GRWD1的表达水平与预测生物标志物之间的相关性，例如肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）。此外，利用 MEXPRESS 网站研究 GRWD1 的 DNA 甲基化水平与病理分期之间的潜在关系。我们利用 TIMER2 网站上提供的“免疫”模块来探索 TCGA 中 GRWD1 的表达水平与所有类型癌症的免疫浸润之间的关系。Pearson相关性分析用于研究GRWD1表达水平与免疫检查点相关基因表达水平的相关性。对于蛋白质表达分析，我们使用 UALCAN 门户提供的 CPTAC 模块来比较邻近正常和肿瘤组织中 GRWD1 的总蛋白和磷酸化蛋白水平。结果. GRWD1在大多数类型癌症的组织中过度表达，其中GRWD1在肾嫌色细胞（KICH）、肾肾乳头状细胞癌（KIRP）和肾肾透明细胞癌（KIRC）组织中的表达水平呈相反趋势， GRWD1 的表达水平仅与 KIRC 肿瘤分期相关。生存分析结果显示，GRWD1的表达水平与六种癌症的总生存期和三种癌症的无病生存期（DFS）显着相关。重要的是，GRWD1 表达水平的增加与 KIRC 患者的预后密切相关。GRWD1的表达水平与几种癌症的免疫细胞浸润呈正相关，GRWD1的表达水平也与TMB呈正相关，MSI 和某些类型癌症中的 DNA 甲基化。京都基因与基因组百科全书 (KEGG) 通路富集分析结果显示，“泛素介导的蛋白水解”、“剪接体”和“核苷酸切除修复”参与了 GRWD1 表达对肿瘤发病机制的影响。结论。这项泛癌分析全面概述了 GRWD1 对多种人类癌症的致癌作用。生物信息学分析结果表明 GRWD1 是一种很有前途的生物标志物，可用于检测、预后和评估多种类型的癌症，并且 GRWD1 可以作为 KIRC 的肿瘤抑制因子。