Comprehensive Analysis of Glutamate‐Rich WD Repeat‐Containing Protein 1 and Its Potential Clinical Significance for Pancancer
Authors: Wu Yumeng , Wu Xuming , Li Yuanyuan , Zhao Wenjing , Yue Yanping , Wu Biao , Liu Jibin , Chen Xudong , Shen Aiguo 
Published: September 2021

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.