HOXB and HOXD genes contribute to the carcinogenic processes in glioblastoma: evidence form a bioinformatics analysis
Year: 2025
Type: article
Abstract: • HOXB2/3/7 and HOXD3/8/9/10/11/13 expression was higher in GBM samples compared to normal samples. • Increased expression of HOXB2/5/8/9/13 was associated with negative effects on survival of patients. • Overexpression of HOXB2/5/9 was linked to inferior progression free survival. • Heightened levels of HOXD4/9, HOXD9/11, and HOXD9/10/11 in GBM were correlated with unfavorable outcomes. • HOXB2 and HOXD3 expression potentially causes resistance to Methotrexate and Z-LLNle-CHO. Glioblastoma is an aggressive cancer that affects the brain. The Homeobox B and D ( HOXB/D ) family has been linked to tumor progression, but their exact mechanism remains unclear. This study aimed to identify critical HOXB/D family members associated with glioblastoma and analyze their expression in glioblastoma using the GEPIA2 database. The study also assessed genetic alterations, their related transcription factors, miRNAs, gene-gene interactions, and correlations between their expression and immune infiltration using databases like cBioPortal, miRNet, GeneMANIA, and GSCA. We showed that HOXB2/3/7 and HOXD3/8/9/10/11/13 expression was higher in glioblastoma samples compared to normal samples. Increased expression of HOXB2/5/8/9/13 was associated with negative effects on overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS), while overexpression of HOXB2/5/9 was linked to inferior PFS. Heightened levels of HOXD4/9, HOXD9/11 , and HOXD9/10/11 expression in glioblastoma patients were correlated with unfavorable outcomes in terms of OS, DSS, and PFS. HOXB/D genes were related to 20 different genes, mainly enriched in the Activation of HOX Genes During Differentiation R-HSA-5619507 pathway. Immune cells were linked to specific genes in glioblastoma, with HOXB2 and HOXD3 expression potentially causing resistance to Methotrexate and Z-LLNle-CHO, HOXB7 indicating sensitivity to Lapatinib but resistance to 18 other small molecules, HOXD8 leading to resistance against 5 small molecules, and upregulated HOXD9, HOXD10 , and HOXD13 suggesting sensitivity to 2, 4, and 9 small molecules, respectively. Taken together, we showed contribution of HOXB and HOXD genes in the carcinogenic processes and proposed them as possible targets for treatment options.
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,740
OpenAlex ID: W4409246223