LRRC8C is a potential diagnostic and prognostic biomarker associated with immune modulation in lower-grade glioma
- 1Department of Neurosurgery, Chinese PLA General Hospital, Beijing, China
- 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Supportive Care Department, Peking University Cancer Hospital & Institute, Beijing, China
- 3Department of Neurosurgery, The Sixth Medical Center of PLA General Hospital, Beijing, China
Abstract
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.
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BibTeX
@article{zhang2026lrrc8c,
title = {{LRRC8C is a potential diagnostic and prognostic biomarker associated with immune modulation in lower-grade glioma}},
author = {Leiming Zhang and Yujie Mu and Wenying Lv and Mei Cui and Jianning Zhang},
journal = {SAGE Open Medicine},
year = {2026},
month = sep,
doi = {10.1177/20503121261488327},
url = {https://doi.org/10.1177/20503121261488327},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - LRRC8C is a potential diagnostic and prognostic biomarker associated with immune modulation in lower-grade glioma
AU - Leiming Zhang
AU - Yujie Mu
AU - Wenying Lv
AU - Mei Cui
AU - Jianning Zhang
PY - 2026
DA - 2026/09/16
JO - SAGE Open Medicine
DO - 10.1177/20503121261488327
UR - https://doi.org/10.1177/20503121261488327
AB - 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.
SN - 2050-3121
ER -