HOXB2 is a prognostic biomarker and correlated with immune infiltration in colorectal cancer and glioma

HOXB2 is a homeobox transcription factor whose dysregulation has been reported in multiple malignancies; however, its clinical relevance and associations with the tumor microenvironment (TME) in colorectal cancer (CRC) and low-grade glioma (LGG) remain incompletely characterized. Public datasets and online platforms (PrognoScan, GEPIA2, TIMER, and Kaplan–Meier Plotter) were integrated to evaluate HOXB2 expression, survival outcomes, and correlations with tumor-infiltrating immune cell estimates in CRC and LGG. Associations between HOXB2 and immune marker genes were further assessed. In vitro, HOXB2 expression and biological effects were examined in glioma cells and normal brain cells using RT-qPCR, CCK-8 proliferation assays, Transwell invasion assays, and Western blotting. HOXB2 knockdown was additionally evaluated in the CRC cell line HT-29 using CCK-8, Transwell invasion assays, and Western blotting. Across three CRC cohorts (GSE17536, GSE17537, and GSE14333), higher HOXB2 expression was significantly associated with poorer overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). In LGG, higher HOXB2 expression was associated with worse OS (HR = 1.8, P = 0.00084) and DFS (HR = 1.5, P = 0.014). TIMER analyses indicated that HOXB2 expression was positively correlated with estimated infiltration levels of B cells, CD4⁺ and CD8⁺ T cells, macrophages, neutrophils, and dendritic cells in colon adenocarcinoma (COAD), rectum adenocarcinoma (READ), and LGG, and was also correlated with marker genes related to tumor-associated macrophages, regulatory T cells, and exhausted T cells. In vitro, HOXB2 expression was higher in glioma cells than in normal brain cells; HOXB2 knockdown reduced glioma cell proliferation and invasion and was accompanied by a decreased p-P65/P65 ratio. In HT-29 cells, HOXB2 knockdown similarly suppressed proliferation and invasion, and Western blotting confirmed effective HOXB2 downregulation. Elevated HOXB2 expression is associated with adverse prognosis and with immune infiltration-related signatures in COAD, READ, and LGG. Together with in vitro findings, these results support HOXB2 as a potential prognostic biomarker and suggest a link between HOXB2 expression, immune-related features, and NF-κB-associated signaling; further pathway-focused and in vivo studies are needed to clarify underlying mechanisms and causality.