Abstract
BACKGROUND: Aberrant glycosylation of proteins plays a critical role in promoting tumor growth and modulating immune responses within the tumor microenvironment. Keratinocyte-associated protein 2 (KRTCAP2) encodes a corresponding protein involved in N-glycosylation, yet its functional and clinical relevance in glioma remains poorly understood. This study aims to elucidate the dual functions of KRTCAP2 in glioma tumorigenesis and immune evasion, and to evaluate its potential as a prognostic biomarker. METHODS: We employed bioinformatics analysis to evaluate KRTCAP2 mRNA expression patterns and immune microenvironment scores in glioma. Multiplex immunohistochemistry (mlHC) was utilized to assess KRTCAP2 protein expression, its association with clinical features, patient prognosis, and immune cell infiltration. To assess the function of KRTCAP2 in regulating glioma cell behaviors and its influence on the tumor immune microenvironment, a set of in vitro functional assay were conducted. Additionally, the relationship between KRTCAP2 expression and therapeutic response was examined using the CelIMiner Cross-Database and apoptosis assays. RESULTS: KRTCAP2 mRNA and protein levels were markedly upregulated in glioma tissues compared to non-tumorous brain tissues. Elevated KRTCAP2 protein expression correlated with adverse clinical characteristics and reduced overall survival. Notably, KRTCAP2 expression showed a significant positive association with the density of infiltrating CD68+ and CD163+ tumor-associated macrophages (TAMs). Depletion of KRTCAP2 significantly inhibited the proliferative, migratory, and invasive capacities of glioma cells, confirming its role as an oncogenic driver. Conversely, KRTCAP2 overexpression promoted these malignant behaviors. Drug sensitivity analysis suggested a role for KRTCAP2 in chemoresistance, with targeted inhibition enhancing glioma cell responsiveness to temozolomide (TMZ). CONCLUSIONS: Our findings identify KRTCAP2 as a novel prognostic biomarker in glioma, with potential utility in predicting immunotherapy response. The study highlights its clinical significance and multifaceted role in shaping an immunosuppressive glioma microenvironment, underscoring KRTCAP2 as a promising therapeutic target.