A Comprehensive Pan-Cancer Analysis Reveals GRB7 as a Potential Diagnostic and Prognostic Biomarker.

Background And Aim: Growth factor receptor-bound protein 7 (GRB7) belongs to a group of adaptor proteins characterized by their conserved multidomain structure. These proteins are involved in cellular signaling pathways that regulate cell growth, proliferation, and differentiation. Alterations in GRB7 expression have been linked to multiple human cancers. However, its role as a diagnostic and prognostic marker remains underexplored. This study aimed to assess the diagnostic and prognostic relevance of GRB7 in a comprehensive pan-cancer analysis.

Materials And Methods:  GRB7 expression across different cancers was evaluated using the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN). The correlation of GRB7 expression with various clinicopathological parameters was assessed by the UALCAN database. Additionally, the Human Protein Atlas (HPA) (https://www.proteinatlas.org/) was used to illustrate the histology of kidney cancer tissues. The correlation between GRB7 expression and prognosis was explored using the Kaplan-Meier plotter, GEPIA, and UALCAN databases. The TIMER database was used to explore the connection between GRB7 expression in tumor tissues and the infiltration of immune cells. Moreover, genetic alterations of the GRB7 gene were detected by the cBioPortal database. Results were validated by the GEO2R database.

Results: GRB7 expression was significantly upregulated in bladder urothelial carcinoma (BLCA), cervical squamous cell carcinoma (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), rectum adenocarcinoma (READ), thyroid carcinoma (THCA), and uterine carcinosarcoma (UCEC). Conversely, it was downregulated in kidney chromophobe (KICH) and kidney renal clear cell carcinoma (KIRC) compared to normal tissues (p<0.001). Further analysis confirmed that GRB7 expression in KICH and KIRC was significantly downregulated across various clinicopathological parameters including stage 3 and stage 4 compared to stage 1. It was also significantly downregulated in 61-80 years compared to 41-60 years patients, as confirmed by the immunohistochemistry of kidney tissues. Prognostic analysis revealed that high GRB7 expression was linked to a better prognosis in KIRC and a poorer prognosis in pancreatic adenocarcinoma (PAAD) patients. In KICH, GRB7 expression showed a significant positive correlation with immune infiltration of B cells, CD8+ T cells, and macrophages. In KIRC, GRB7 was positively correlated with immune infiltration of B cells and CD4+ cells. However, in PAAD it was negatively correlated with immune infiltration of macrophages. These findings were validated by gene expression profiling from the Gene Expression Omnibus (GEO) database, confirming a significant GRB7 downregulation in KICH and KIRC and an upregulation in PAAD compared to normal samples.  Conclusion: GRB7 shows potential as a biomarker in both diagnosing and predicting outcomes for various cancers. It may serve as a diagnostic marker for KICH, a prognostic marker for PAAD, and both a diagnostic and prognostic marker for KIRC, making GRB7 a target for future research and therapeutic approaches in oncology.