An Integrative Analysis Identifying RAB40C as an Oncogenic Immune Protein and Prognostic Marker of Lung Squamous Cell Carcinoma

BACKGROUND: RAB40C, a member of the Ras oncogene family, is a protein with GTPase and GTP-binding activity and is also predicted to be important in immunomodulation. However, the link between RAB40C and lung squamous cell carcinoma (LUSC) has not yet been elucidated. Exploring the relationship between RAB40C and LUSC could help expand the repertoire of immunotherapeutic targets for LUSC and provide more effective therapeutic options for LUSC patients, which behalf of our aim for our study. METHODS: We analyzed the RAB40C expression in different tumor types and stages based on the TCGA database. Subsequently, we explored the differences in RAB40C expression in LUSC versus paracancerous tissues through immunohistochemical analysis. The prognostic value of RAB40C was assessed by Cox regression and Kaplan-Meier analysis. Gene set enrichment analysis-based RAB40C impact pathways and the correlation between RAB40C expression and immune infiltration were obtained using the TIMER2.0 and the CIBERSORT analytical tools. Tumor mutational load and microsatellite instability (MSI) were assessed by the Spearman correlation analysis. Finally, the close association of RAB40C with LUSC was explored by correlating immune cell infiltration with immunomodulator expression, assessing risk scores in combination with other factors, and analyzing prognostic nomogram. RESULTS: The expression of RAB40C was significantly elevated in LUSC. RAB40C expression was significantly associated with immune factors, immune-related pathways, and MSI. Moreover, RAB40C significantly negatively correlated with LUSC-associated immune infiltrating cells, CD4 memory-activated cells, γδ T cells, M1-like macrophages, and the immune regulator CD28, while it positively associated with the activation of Tregs and natural killer cells. Further, a risk model constructed from RAB40C and its associated immune genes showed that RAB40C might be an independent prognostic factor for LUSC. CONCLUSION: RAB40C can be used as an effective prognostic biomarker and a potential immunotherapeutic target for the treatment of LUSC.