A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironment

BackgroundThe Homeobox (HOX) gene family are conserved transcription factors that are essential for embryonic development, oncogenesis, and cancer suppression in biological beings. Abnormally expressed HOX genes in cancers are directly associated with prognosis.MethodsPublic databases such as TCGA a...

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Main Authors: Yuanhui Wang, Jie Gao, Ziyi Ren, Ziyi Shen, Wei Gu, Qinyi Miao, Xiaomeng Hu, Yan Wu, Wei Liu, Jia Jia, Yi Cai, Chunpeng (Craig) Wan, Lei Sun, Tingdong Yan
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Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1521652/full
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author Yuanhui Wang
Jie Gao
Ziyi Ren
Ziyi Shen
Wei Gu
Qinyi Miao
Xiaomeng Hu
Xiaomeng Hu
Yan Wu
Yan Wu
Wei Liu
Jia Jia
Jia Jia
Yi Cai
Chunpeng (Craig) Wan
Lei Sun
Tingdong Yan
Tingdong Yan
author_facet Yuanhui Wang
Jie Gao
Ziyi Ren
Ziyi Shen
Wei Gu
Qinyi Miao
Xiaomeng Hu
Xiaomeng Hu
Yan Wu
Yan Wu
Wei Liu
Jia Jia
Jia Jia
Yi Cai
Chunpeng (Craig) Wan
Lei Sun
Tingdong Yan
Tingdong Yan
author_sort Yuanhui Wang
collection DOAJ
description BackgroundThe Homeobox (HOX) gene family are conserved transcription factors that are essential for embryonic development, oncogenesis, and cancer suppression in biological beings. Abnormally expressed HOX genes in cancers are directly associated with prognosis.MethodsPublic databases such as TCGA and the R language were used to perform pan-cancer analyses of the HOX family in terms of expression, prognosis, and immune microenvironment. The HOX score was defined, and potential target compounds in cancers were predicted by Connective Map. Immunohistochemistry was employed to validate protein expression levels. Gene knockdowns were used to verify the effects of HOXB7 and HOXC6 on the proliferation and migration of lung adenocarcinoma (LUAD) cells.ResultsHOX genes play different roles in different cancers. Many HOX genes, especially HOXB7 and HOXC6, have higher expression and lower overall survival in specific cancers and are predicted as risk factors. The high expression of most HOX genes is mainly related to immune subtypes C1-C4 and C6. Potential anti-tumor compounds for down-regulating HOX gene expression were identified, such as HDAC inhibitors and tubulin inhibitors. LUAD Cell migration and proliferation were inhibited when HOXB7 or HOXC6 was knocked down.ConclusionsMany HOX genes may act as both oncogenes and tumor suppressor genes, necessitating precision medicine based on specific cancers. The HOX gene family plays a crucial role in the development of certain cancers, and their expression patterns are closely related to cancer prognosis and the tumor microenvironment (TME), which may affect cancer prognosis and response to immunotherapy. Compounds that are negatively correlated with the expression levels of the HOX family in various cancers, such as HDAC inhibitors, are potential anti-cancer drugs. HOXB7 and HOXC6 may serve as potential targets for cancer treatment and the development of targeted compounds in the future.
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spelling doaj-art-15c3b331e9b44b5088954ac989e8ab9a2025-02-06T05:21:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-02-011510.3389/fonc.2025.15216521521652A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironmentYuanhui Wang0Jie Gao1Ziyi Ren2Ziyi Shen3Wei Gu4Qinyi Miao5Xiaomeng Hu6Xiaomeng Hu7Yan Wu8Yan Wu9Wei Liu10Jia Jia11Jia Jia12Yi Cai13Chunpeng (Craig) Wan14Lei Sun15Tingdong Yan16Tingdong Yan17School of Life Sciences, Shanghai University, Shanghai, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaTranslational Medicine Center, Zhejiang Xinda Hospital, School of Medicine&Nursing, Huzhou University, Huzhou, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaTranslational Medicine Center, Zhejiang Xinda Hospital, School of Medicine&Nursing, Huzhou University, Huzhou, ChinaUniversity and College Key Lab of Natural Product Chemistry and Application in Xinjiang, School of Chemistry and Environmental Science, Yili Normal University, Yining, ChinaTranslational Medicine Center, Zhejiang Xinda Hospital, School of Medicine&Nursing, Huzhou University, Huzhou, ChinaUniversity and College Key Lab of Natural Product Chemistry and Application in Xinjiang, School of Chemistry and Environmental Science, Yili Normal University, Yining, ChinaUniversity and College Key Lab of Natural Product Chemistry and Application in Xinjiang, School of Chemistry and Environmental Science, Yili Normal University, Yining, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaTranslational Medicine Center, Zhejiang Xinda Hospital, School of Medicine&Nursing, Huzhou University, Huzhou, ChinaKey Laboratory of Molecular Target & Clinical Pharmacology and the State & National Medical Products Administration (NMPA) Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaJiangxi Key Laboratory for Postharvest Technology and Nondestructive Testing of Fruits and Vegetables, College of Agronomy, Jiangxi Agricultural University, Nanchang, ChinaDepartment of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaSchool of Life Sciences, Shanghai University, Shanghai, ChinaTranslational Medicine Center, Zhejiang Xinda Hospital, School of Medicine&Nursing, Huzhou University, Huzhou, ChinaBackgroundThe Homeobox (HOX) gene family are conserved transcription factors that are essential for embryonic development, oncogenesis, and cancer suppression in biological beings. Abnormally expressed HOX genes in cancers are directly associated with prognosis.MethodsPublic databases such as TCGA and the R language were used to perform pan-cancer analyses of the HOX family in terms of expression, prognosis, and immune microenvironment. The HOX score was defined, and potential target compounds in cancers were predicted by Connective Map. Immunohistochemistry was employed to validate protein expression levels. Gene knockdowns were used to verify the effects of HOXB7 and HOXC6 on the proliferation and migration of lung adenocarcinoma (LUAD) cells.ResultsHOX genes play different roles in different cancers. Many HOX genes, especially HOXB7 and HOXC6, have higher expression and lower overall survival in specific cancers and are predicted as risk factors. The high expression of most HOX genes is mainly related to immune subtypes C1-C4 and C6. Potential anti-tumor compounds for down-regulating HOX gene expression were identified, such as HDAC inhibitors and tubulin inhibitors. LUAD Cell migration and proliferation were inhibited when HOXB7 or HOXC6 was knocked down.ConclusionsMany HOX genes may act as both oncogenes and tumor suppressor genes, necessitating precision medicine based on specific cancers. The HOX gene family plays a crucial role in the development of certain cancers, and their expression patterns are closely related to cancer prognosis and the tumor microenvironment (TME), which may affect cancer prognosis and response to immunotherapy. Compounds that are negatively correlated with the expression levels of the HOX family in various cancers, such as HDAC inhibitors, are potential anti-cancer drugs. HOXB7 and HOXC6 may serve as potential targets for cancer treatment and the development of targeted compounds in the future.https://www.frontiersin.org/articles/10.3389/fonc.2025.1521652/fullHomeobox familypan-cancerimmune microenvironmentprognosisHOXB7HOXC6
spellingShingle Yuanhui Wang
Jie Gao
Ziyi Ren
Ziyi Shen
Wei Gu
Qinyi Miao
Xiaomeng Hu
Xiaomeng Hu
Yan Wu
Yan Wu
Wei Liu
Jia Jia
Jia Jia
Yi Cai
Chunpeng (Craig) Wan
Lei Sun
Tingdong Yan
Tingdong Yan
A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironment
Frontiers in Oncology
Homeobox family
pan-cancer
immune microenvironment
prognosis
HOXB7
HOXC6
title A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironment
title_full A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironment
title_fullStr A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironment
title_full_unstemmed A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironment
title_short A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironment
title_sort pan cancer analysis of homeobox family expression characteristics and latent significance in prognosis and immune microenvironment
topic Homeobox family
pan-cancer
immune microenvironment
prognosis
HOXB7
HOXC6
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1521652/full
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