LRRC8C is a potential diagnostic and prognostic biomarker associated with immune modulation in lower-grade glioma

Objectives To investigate the diagnostic and prognostic value and immune-related associations of LRRC8C, a volume-regulated anion channel (VRAC) subunit, in lower-grade glioma (LGG). Background LGG often progresses to high-grade malignancy, complicating diagnosis and treatment. LRRC8C, a VRAC subunit, influences immune regulation in various cancers, but its role in LGG remains uncharacterized. Methods Using uniformly reprocessed transcriptomic and clinical data from the TCGA-LGG and GTEx cohorts (UCSC Xena Toil dataset), we performed differential expression, survival, gene set enrichment (GSEA), and immune infiltration analyses of LRRC8C in LGG. Results LRRC8C was significantly upregulated in LGG tissues with potential diagnostic value (AUC = 0.821, 95% CI: 0.801–0.842). Higher LRRC8C expression was associated with shorter overall survival (OS) and progression-free interval (PFI); this association was attenuated after adjustment for age and IDH status (multivariate Cox P = 0.054), indicating that LRRC8C overlaps with—rather than acts independently of—established molecular factors. This pattern was externally validated in the Chinese Glioma Genome Atlas (CGGA) cohort (n = 271). GSEA showed enrichment in immune and vascular pathways. Cross-validation with seven deconvolution algorithms confirmed robust positive correlations between LRRC8C expression and infiltration of CD8+ T cells, B cells, neutrophils, and dendritic cells, whereas the natural killer (NK) cell association was not robust. These findings are correlative and require experimental confirmation. Conclusion LRRC8C is a potential diagnostic biomarker and prognostic indicator in LGG, although its prognostic value is not fully independent of established molecular factors. Its immune-related associations are hypothesis-generating and require experimental verification.