Prognostic and immunological role of LASP2 in clear cell renal cell carcinoma

Genes Genomics. 2024 Dec 23. doi: 10.1007/s13258-024-01612-9. Online ahead of print.

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) represents a common renal carcinoma subtype influenced by the immune microenvironment. LIM and SH3 Protein 2 (LASP2), an actin-binding protein within the nebulin family, contributes to cellular immunity and adhesion mechanisms.

Objective: This study aimed to clarify the immunological and prognostic relevance of LASP2 in ccRCC.

Methods: Using clinical and expression data from TCGA, LASP2 expression levels were analyzed alongside clinicopathological features in ccRCC patients. Validation was conducted through real-world samples and tissue microarrays. Comprehensive analysis using online databases examined genetic mutations, DNA methylation patterns, and immune microenvironment characteristics. Gene set enrichment analysis (GSEA) provided insights into LASP2's potential mechanisms in ccRCC.

Results: LASP2 expression was notably reduced and correlated with adverse clinicopathological features and prognosis in ccRCC patients. Prognostic associations were identified across multiple CpG DNA methylation sites. LASP2 levels showed significant correlations with immune cell infiltration and checkpoint genes, including PDCD1 and CTLA4. GSEA findings highlighted LASP2's enrichment within metabolic pathways and signaling networks, such as fatty acid metabolism, TGF-β signaling, and epithelial-mesenchymal transition.

Conclusion: LASP2 emerged as an immune-associated biomarker linked to poorer survival outcomes in ccRCC, suggesting its potential as a novel anti-cancer target and prognostic indicator in ccRCC.

Keywords: Clear cell renal cell carcinoma; Immune microenvironment; LASP2; Prognosis.