Biom-16. Integrative Transcriptomic and Single-Cell Analysis Reveals Rnf135 as a Prognostic and Immunological Biomarker in Glioblastoma

INTRODUCTION Glioblastoma is among the most aggressive primary brain tumors, despite advances in surgical and adjuvant therapies, GBM patients often surviving less than two years after diagnosis. The exploration of new therapeutic targets and novel genes to alter the prognosis of GBM patients holds significant importance. Here, we identified RNF135, a ring-finger protein-encoding gene, as a potential immune-related biomarker and therapeutic target in GBM. Method: We integrated high-throughput RNA-sequencing data from multiple public databases. Bulk transcriptomic data were used for survival analyses and gene function analysis. Immune infiltration was assessed using MCP-counter, xCell and ssGSEA. Single-cell RNA-sequencing data from GSE131928 were utilized to provide cellular resolution of RNF135 expression among tumor-associated macrophage subtypes, bulk RNA-sequencing data from the IVY were used to validate its spatial distribution within distinct anatomical regions of GBM. Drug sensitivity analysis was conducted to explore effective treatment options for the RNF135-high patient group. RESULTS High RNF135 expression was strongly associated with poor overall survival. Immune deconvolution analyses revealed that RNF135-high tumors exhibit increased infiltration of immune cells. Single-cell RNA sequencing data showed that RNF135 is enriched in aggressive TAM subsets, specifically monocyte-derived TAMs and proliferative TAMs. Validation using the IVY dataset confirmed that RNF135 is predominantly expressed in highly vascularized tumor niches. GSEA demonstrated significant enrichment of inflammatory and oncogenic pathways—including KRAS, IL6-JAK-STAT3, and TNF-ααα-NF-κκκB—supporting RNF135’s involvement in tumor progression. Drug sensitivity analyses indicated that RNF135-high tumors may be more responsive to MEK inhibition (e.g., Selumetinib), aligning with the observed enrichment of KRAS-driven pathways. CONCLUSION RNF135 could serve as both prognostic marker and potential target for precision therapy. Further comprehensive experimental validation and clinical investigations are warranted to explore RNF135-targeted therapeutic strategies in GBM.