Table 4.
Biological role and clinical implications of HOX genes in cancer
| Deregulated HOX genes | Target | Cancer | Clinical Utility | References | |
|---|---|---|---|---|---|
| HOX gene as a prognostic marker | |||||
| HOXA5↓ | CDKN1A | Non-small cell lung cancer | Positively correlated with TNM staging | Zhang et al. 2015 | |
| HOXA5, HOXA9↑ | - | Acute myeloid leukemia | Decreases the remission rate | Zhao et al. 2015 | |
| HOXA10↑ | MMP3 | Bladder cancer | Positively associated with pathological grade and clinical stage | Liu et al. 2019 | |
| HOXA13↑ | - | Lung squamous cancer | Positively correlated with TNM stage | Zhang et al. 2017 | |
| HOXA13↑ | - | Bladder cancer | Positively correlated with lymphatic metastasis, pathological grade, and TNM stage | Hu et al. 2017 | |
| HOXB9↑ | - | Laryngeal squamous cell carcinoma | Positively correlated with histological grade | Sun et al. 2017 | |
| HOXC6↑ | Ki67 | Nasopharyngeal carcinoma | Significantly associated with tumor stage and advanced tumor status | Chang et al. 2017 | |
| HOXC9↑ | - | Colorectal cancer | Positively correlated with tumor stage, distant metastasis, and venous invasion | Hu et al. 2019 | |
| HOXC9↑ | - | Gastric cancer | Positively correlated with tumor size, lymphatic invasion, and lymph node metastasis | Zhao et al. 2020 | |
| HOXC10↑ | - | Thyroid cancer | Positively correlated with advanced and poor pathological stage | Feng et al. 2015 | |
| HOXC10↑ | - | Glioma | Positively associated high grading; induces immunosuppressive genes | Li et al. 2018 | |
| Role of HOX genes in therapy resistance | |||||
| HOXA5↑ | - | Acute myeloid leukemia | Provides resistance to cytarabine | Li et al. 2015 | |
| HOXA9↑ | BCL2 | Glioblastoma | Confers resistance to temozolomide | Pojo et al. 2015 | |
| HOXA10↑ | PTEN | Colorectal cancer | Provides resistance to 5-Fluorouracil | Yuan et al. 2018 | |
| HOXA11↓ | - | Glioblastoma | Confers resistance to radiation and temozolomidetherapy | Se et al. 2017 | |
| HOXA13↑ | - | Hepatocellular carcinoma | Provides resistance to sorafenib | Quagliata et al. 2018 | |
| HOXA13↑ | MRP1, DHRS2 | Gastric cancer | Provides resistance to 5-Fluorouracil | Han et al. 2018 | |
| HOXB cluster genes↑ | - | Breast cancer | Provides tamoxifen resistancce | Yang et al. 2018 | |
| HOXB13↑ | ERα, IL-6 | Breast cancer | Promotes tamoxifen resistancce | Shah et al. 2013 | |
| HOXC6↑ | BCL2 | Head and neck squamous cell carcinoma | Confers paclitaxel therapy resistance | Moon et al. 2012 | |
| HOXC8↑ | TGF-β1 | Non-small cell lung cancer | Provides cisplatin resistance | Liu et al. 2018 | |
| HOXC10↓ | - | Breast cancer | Confers resistance to aromatase inhibitors | Pathiraja et al. 2014 | |
| HOXD8↑ | - | Epithelial ovarian cancer | Promotes cisplatin therapy resistance | Sun et al. 2018 | |
| HOX gene as a biomarker for predicting disease recurrence | |||||
| HOXC10↑ | - | Gastric cancer | Positively associated with hepatic and peritoneal recurrence | Miwa et al. 2019 | |
| HOXA9↓ | - | Non-small cell lung cancer | Provides disease recurrence | Hwang et al. 2015 | |
| HOXA4/HOXB3↑ | - | High-grade serous ovarian carcinoma | Biomarker for recurrence after primary cytoreductive surgery and first-line adjuvant chemotherapy | Miller et al. 2018 | |
| HOXB7↑ | bFGF | Hepatocellular carcinoma | Provides disease recurrence | Wang et al. 2017 | |
NOTE: DHRS2, dehydrogenase reductase 2; CST1, cystatin SN; ↑, upregulated; ↓, downregulated