Identification and validation of AFAP1L1 as an immune-related prognostic biomarker in clear cell renal cell carcinoma.

BACKGROUND

Clear cell renal cell carcinoma (ccRCC) accounts for over 75% of all renal cancer and contributes significantly to cancer-associated mortality. This study aims to identify a new ccRCC biomarker.

METHODS

Univariate and multivariate Cox regression models were performed for prognostic analysis. Differentially expressed genes (DEGs) were identified based on high and low expression AFAP1L1 groups. Functional enrichment analysis was conducted on the DEGs. Immunoassays were conducted on immune checkpoints, immune cells, and other components. Single-cell expression of AFAP1L1, along with associated pseudo-temporal trajectory analyses, was evaluated. The Connectivity Map was employed to identify potentially small-molecules. AFAP1L1 mRNA expression was measured via quantitative real-time PCR (qRT-PCR) experiment.

RESULTS

AFAP1L1 was significantly upregulated in training cohort and qRT-PCR, and lower expression level was correlated with shorter overall survival, which was also confirmed in E-MTAB-1980 and CPTAC validation cohorts. The upregulated DEGs were primarily involved in signaling pathways, nephron development, and transporter activity. AFAP1L1 was positively related with neutrophils and macrophages. AFAP1L1 exhibited a relatively higher expression level in endothelial cells at the single-cell level. Five potential therapeutic agents targeting ccRCC were identified.

CONCLUSIONS

AFAP1L1 may impact the ccRCC development and progression, acting as an immune-related prognostic marker for ccRCC.