HOXB and HOXD genes contribute to the carcinogenic processes in glioblastoma: evidence form a bioinformatics analysis

Purpose: 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. Material and methods: This study aimed to identify critical HOXB/D family members associated with glioblastoma a...

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Main Authors: Mohsen Ahmadi, Maryam Bazrgar, Saeedeh Akhavan, Mohadeseh Fathi, Pegah Mousavi, Soudeh Ghafouri-Fard
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cancer Treatment and Research Communications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468294225000607
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author Mohsen Ahmadi
Maryam Bazrgar
Saeedeh Akhavan
Mohadeseh Fathi
Pegah Mousavi
Soudeh Ghafouri-Fard
author_facet Mohsen Ahmadi
Maryam Bazrgar
Saeedeh Akhavan
Mohadeseh Fathi
Pegah Mousavi
Soudeh Ghafouri-Fard
author_sort Mohsen Ahmadi
collection DOAJ
description Purpose: 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. Material and methods: 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. Results: 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. Conclusion: Taken together, we showed contribution of HOXB and HOXD genes in the carcinogenic processes and proposed them as possible targets for treatment options.
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spelling doaj-art-7a4f913db2d541758bd3c4a628810ff82025-08-20T03:08:42ZengElsevierCancer Treatment and Research Communications2468-29422025-01-014310092310.1016/j.ctarc.2025.100923HOXB and HOXD genes contribute to the carcinogenic processes in glioblastoma: evidence form a bioinformatics analysisMohsen Ahmadi0Maryam Bazrgar1Saeedeh Akhavan2Mohadeseh Fathi3Pegah Mousavi4Soudeh Ghafouri-Fard5Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranNeuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University (IAU), Tehran, IranStudent Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranMolecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; Corresponding authors.Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Corresponding authors.Purpose: 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. Material and methods: 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. Results: 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. Conclusion: Taken together, we showed contribution of HOXB and HOXD genes in the carcinogenic processes and proposed them as possible targets for treatment options.http://www.sciencedirect.com/science/article/pii/S2468294225000607Bioinformatics analysisThe Homeobox B familyGlioblastomaBiomarkerPrognosisImmune infiltration
spellingShingle Mohsen Ahmadi
Maryam Bazrgar
Saeedeh Akhavan
Mohadeseh Fathi
Pegah Mousavi
Soudeh Ghafouri-Fard
HOXB and HOXD genes contribute to the carcinogenic processes in glioblastoma: evidence form a bioinformatics analysis
Cancer Treatment and Research Communications
Bioinformatics analysis
The Homeobox B family
Glioblastoma
Biomarker
Prognosis
Immune infiltration
title HOXB and HOXD genes contribute to the carcinogenic processes in glioblastoma: evidence form a bioinformatics analysis
title_full HOXB and HOXD genes contribute to the carcinogenic processes in glioblastoma: evidence form a bioinformatics analysis
title_fullStr HOXB and HOXD genes contribute to the carcinogenic processes in glioblastoma: evidence form a bioinformatics analysis
title_full_unstemmed HOXB and HOXD genes contribute to the carcinogenic processes in glioblastoma: evidence form a bioinformatics analysis
title_short HOXB and HOXD genes contribute to the carcinogenic processes in glioblastoma: evidence form a bioinformatics analysis
title_sort hoxb and hoxd genes contribute to the carcinogenic processes in glioblastoma evidence form a bioinformatics analysis
topic Bioinformatics analysis
The Homeobox B family
Glioblastoma
Biomarker
Prognosis
Immune infiltration
url http://www.sciencedirect.com/science/article/pii/S2468294225000607
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