RHEBL1 is the Rheb branch of the GTPase proteins that are members of the Ras superfamily. However, it remains unclear how it is relevant to the tumour immune microenvironment. This research evaluates the expression of RHEBL1 employing data from the Cancer Genome Atlas (TCGA) and Genotypic Tissue Expression (GTEx) databases. TCGA cohort was employed to identify the clinical characteristics and prognostic effect of RHEBL1. R Package clusterProfiler was employed to execute Gene Set enrichment analysis (GSEA) on RHEBL1. The association between RHEBL1 and immune cell infiltration (ICI) score was analyzed by employing TCGA samples copied from the public platform and TIMER2 database. Correlation analysis of IC50 values of 192 anti-cancer medicine copied from the Genomics of Drug Sensitivity in Cancer (GDSC) database. In the end, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was employed to assessing RHEBL1 expression level in tumours and paracancerous tissues of colon cancer patients. It was found that the overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression free interval (PFI) progression of colon adenocarcinoma (COAD) are highly related with high expression of RHEBL1 (p < 0.05). In addition, pathways related to immune regulation were closely involved in RHEBL1 expression. Furthermore, the levels of tumour-associated macrophage (TAM) and CD8 + T-cell infiltration were positively correlated with the expression of RHEBL1 in TCGA Pan-cancer samples. Patients with high RHEBL1 expression may be more sensitive to treatment with 5-FU, ABT737, Afuresertib, AGI-5198, AGI-6780, and Alisertib (p < 0.05) and could benefit from these chemotherapeutic agents. In vitro experimental results showed that RHEBL1 was significantly increased in COAD (p < 0.05). These findings indicate that RHEBL1 is an oncogene for multiple tumours and an important factor affecting tumour prognosis. Pan-cancer samples suggested that high RHEBL1 expression facilitates TAM infiltration and is correlated with tumour immunosuppressive status (TCGA). High expression of RHEBL1 may benefit from the therapy of 5-FU, ABT737, Afuresertib, AGI-5198, AGI-6780, and Alisertib.
Keywords: Drug sensitivity in cancer; Immune cell infiltration; RHEBL1; Tumour immune microenvironment.
© 2025. The Author(s).