Informatics in Medicine Unlocked (Jan 2024)
GLIPR2 emerges as a potential predictor of prognosis for renal clear cell carcinoma, exhibiting substantial relevance with cellular metastasis and CD8+ T cell infiltration
Abstract
Background: The incidence of renal clear cell carcinoma (ccRCC) is steadily growing, and cellular metastasis and extensive infiltration of CD8+ T cells are the primary factors contributing to its undesirable prognosis. GLIPR2 (GLI pathogenesis related 2) belongs to the PR-1 family, and it was upregulated in hepatocellular carcinoma, playing a role in the regulation of epithelial cell to mesenchymal transition (EMT). However, its involvement in ccRCC remains unknown. Methods: Genes associated with tumor metastasis and CD8+ T cell levels were identified through weighted gene coexpression network analysis (WGCNA) leveraging the TCGA and GEO databases. Afterwards we follow survival, univariate Cox regression, receiver operating characteristic (ROC) and drug susceptibility analyses confirmed the most influential gene. Further exploration of its molecular, metastatic, and immune properties was carried out through bioinformatics analysis and experimental validation. Results: Initially, GLIPR2 was identified as the most influential gene via WGCNA. Our findings indicated that GLIPR2 exhibited high expression levels in ccRCC and metastatic ccRCC, and its over-expression is significantly correlated with an unfavorable prognosis. Competing endogenous RNAs (CeRNA) network analysis offered insights into the potential regulatory mechanisms governing its expression. Pathway enrichment analysis revealed the involvement of GLIPR2 in multiple pathways intertwined with immune and cellular metastasis. Meanwhile, experiments provided confirmation that GLIPR2 may facilitate the metastasis of ccRCC through EMT. However, the specific mechanisms by which GLIPR2 regulated EMT to promote invasion and migration in ccRCC required in-depth exploration. Single-cell sequencing, immune infiltration, immune survival, and immunotherapy analysis demonstrated the close association between GLIPR2 and CD8+ T cells in ccRCC, as well as its potential for immunotherapeutic intervention. Conclusions: The upregulation of GLIPR2 in ccRCC is associated with cellular metastasis and enrichment of CD8+ T cells. Herein, it may hold promising potential as a predictive independent biomarker for ccRCC metastasis, immune infiltration, and prognosis.
