ARPC5 acts as a potential prognostic biomarker that is associated with cell proliferation, migration and immune infiltrate in gliomas.

ABSTRACT

BACKGROUND: Gliomas are the most common malignant brain tumors, with powerful invasiveness and an undesirable prognosis. Actin related protein 2/3 complex subunit 5 (ARPC5) encodes a component of the Arp2/3 protein complex, which plays a significant role in regulating the actin cytoskeleton. However, the prognostic values and biological functions of ARPC5 in gliomas remain unclear. METHODS: Based on the TCGA, GEO, HPA, and UALCAN database, we determined the expression of ARPC5 in glioma. The results were verified by immunohistochemistry and Western blot analysis of glioma samples. Moreover, Kaplan-Meier curves, ROC curves, Cox regression analyses, and prognostic nomograms were used to observe the correlation between the ARPC5 expression and the prognosis of glioma patients. GO and KEGG enrichment analyses were conducted to identify immune-related pathways involved with the differential expression of ARPC5. Subsequently, the TCGA database was used to estimate the relationship between ARPC5 expression and immunity-related indexes, such as immune scores, infiltrating immune cells, and TMB. The TCIA database was used to assess the correlation between ARPC5 with immunotherapy. The association between ARPC5 and T cells marker CD3 was also evaluated through immunohistochemistry methods. The correlation between ARPC5 and T cell, as well as the prognosis of patients, was also evaluated using immunological methods. Moreover, the effect of ARPC5 on the biological characteristics of LN229 and U251 cells was determined by MTT, clone formation, and transwell migration assay. RESULTS: The high degree of ARPC5 was correlated with worse prognosis and unfavorable clinical characteristics of glioma patients. In the analysis of GO and KEGG, it is shown that ARPC5 was strongly correlated with multiple immune-related signaling pathways. The single-cell analysis revealed that ARPC5 expression was increased in astrocytes, monocytes and T cells. In addition, ARPC5 expression was strongly associated with immune scores, infiltrating immune cells, TMB, MSI, immune biomarkers, and immunotherapy. In experimental analysis, we found that ARPC5 was significantly overexpressed in gliomas and closely correlated with patient prognosis and CD3 expression. Functionally, the knockout of ARPC5 significantly reduced the proliferation and invasion of LN229 and U251 cells. CONCLUSIONS: Our study revealed that the high expression level of ARPC5 may serve as a promising prognostic biomarker and be associated with tumor immunity in glioma.