Pan-Cancer Analysis Identifies a Ras-Related GTPase as a Potential Modulator of Cancer

Ras signaling regulates many cellular processes in cancer development. While well-known Ras-related oncogenes, such as KRAS, have been extensively explored, the role of other Ras-related genes in cancer remains poorly studied. Dexamethasone-induced Ras-related protein 1 (RASD1), a member of the Ras superfamily, is widely expressed across various tissues and is involved in inhibiting cell growth and inducing apoptosis, suggesting a potential role as a tumor suppressor. Here, we investigated RASD1 expression across multiple tissues and cancers, utilizing data from The Cancer Genome Atlas (TCGA), Human Protein Atlas, and Genotype-Tissue Expression (GTEx) databases. Our analysis revealed a significant downregulation of RASD1 mRNA expression in several cancer types compared to normal tissues, correlating with low levels of promoter methylation. Interestingly, high RASD1 expression correlated with a favorable prognosis in multiple cancers. Immune cell infiltration analysis indicated that elevated RASD1 expression is associated with an increased infiltration of CD4⁺ T cells and myeloid-derived dendritic cells in cancer. Furthermore, the expression of genes exhibiting similar expression patterns as RASD1 suggest that RASD1 may play a role in interleukin-4-mediated apoptosis and could regulate the transcription of the phosphatase and tensin homolog (PTEN) gene. Overall, these findings suggest that RASD1 may modulate immune signaling and tumor suppressive pathways.