Table 1.
The role of HOX genes in the development of human cancer
| Cluster | HOX genes | Chromosomal location | Cancer | Aberrant expression | References |
|---|---|---|---|---|---|
| Oncogenic HOX genes | |||||
| HOXA cluster | HOXA1 | chr7:27,092,993–27,096,000 | Gastric cancer, human mammary carcinoma, prostate cancer | ↑ | Hou et al. 2012; Mohankumar et al. 2007; Wang et al. 2015; Yuan et al. 2016 |
| HOXA10 | chr7:27,170,605–27,174,320 | Bladder cancer, colorectal cancer, acute myeloid leukemia, laryngeal squamous cell cancer, pancreatic cancer | ↑ | Cui et al. 2014; Guo et al. 2020; Li et al. 2020a; Liu et al. 2019a; Yuan et al. 2018 | |
| HOXA13 | chr7:27,194,364–27,200,091 | Gastric cancer, lung squamous cancer, bladder cancer, kidney renal clear-cell carcinoma, glioma | ↑ | Cui et al. 2020; Duan et al. 2015; Han et al. 2018; Hu et al. 2017; Zhang et al. 2017 | |
| HOXB cluster | HOXB2 | chr17:48,542,655–48,544,989 | Glioblastoma | ↑ | Li et al. 2020b |
| HOXB3 | chr17:48,550,006–48,590,272 | High-grade serous ovarian carcinoma | ↑ | Miller et al. 2018 | |
| HOXB4 | chr17:48,575,507–48,578,350 | Chronic myelogenous leukemia | ↑ | Wang et al. 2016 | |
| HOXB5 | chr17:48,591,257–48,593,961 | Breast cancer, gastric cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, pancreatic cancer, retinoblastoma, hepatocellular carcinoma | ↑ | Gao et al. 2020; Hong et al. 2015; Lee et al. 2015; Lee et al. 2020; Su et al. 2020; Xu et al. 2018; Zhang et al. 2018 | |
| HOXB7 | chr17:48,607,232–48,611,017 | Esophageal squamous cell carcinoma, gastric cancer, glioma, cutaneous squamous cell carcinoma, breast cancer, pancreatic cancer, hepatocellular carcinoma, acute lymphoblastic leukemia, multiple myeloma, lung adenocarcinoma, colorectal cancer | ↑ | Gao and Chen 2018; He et al. 2017; Huo et al. 2019; Li et al. 2015; Liao et al. 2011; Liu et al. 2015a; Storti et al. 2011; Tsuboi et al. 2017; Wang et al. 2017; Zhong et al. 2019; Zhuang et al. 2015 | |
| HOXB8 | chr17:48,612,346–48,615,292 | Colorectal cancer, osteosarcoma | ↑ | Guo et al. 2019; Wang et al. 2019a | |
| HOXC cluster | HOXC6 | chr12:54,028,440–54,030,823 | Gastric cancer, nasopharyngeal carcinoma, cervical cancer, glioblastoma, head and neck squamous cell carcinoma | ↑ | Chang et al. 2017; Jung et al. 2020; Moon et al. 2012; Wang et al. 2019b; Yang et al. 2019 |
| HOXC8 | chr12:54,008,985–54,012,769 | Laryngeal squamous cell carcinoma, glioma, cervical cancer, non-small cell lung cancer | ↑ | de Barros E Lima Bueno et al. 2016; Huang et al. 2018; Liang et al. 2018; Liu et al. 2018 | |
| HOXC9 | chr12:53,995,509–54,003,298 | Colorectal cancer, gastric cancer, neuroblastoma, glioblastoma | ↑ | Hu et al. 2019; Kocak et al. 2013; Xuan et al. 2016; Zhao et al. 2020 | |
| HOXC10 | chr12:53,985,146–53,990,279 | Thyroid cancer, gastric cancer, glioma, breast cancer | ↑ | Feng et al. 2015; Kim et al. 2019; Li et al. 2018; Miwa et al. 2019; Sadik et al. 2016 | |
| HOXC11 | chr12:53,973,126–53,977,643 | Renal cell carcinoma | ↑ | Liu et al. 2015b | |
| HOXD cluster | HOXD3 | chr2:176,160,891–176,173,085 | Non-small cell lung cancer | ↑ | Miyazaki et al. 2002 |
| HOXD4 | chr2:176,151,550–176,153,226 | Gastric adenocarcinoma | ↑ | Liu et al. 2019b | |
| HOXD9 | chr2:176,122,719–176,124,937 | Gastric cancer | ↑ | Xiong et al. 2020 | |
| HOXD11 | chr2:176,104,216–176,109,754 | Laryngeal squamous cell carcinoma | ↑ | de Barros E Lima Bueno et al. 2016 | |
| Tumor suppressor HOX genes | |||||
| HOXA cluster | HOXA3 | chr7:27,107,012–27,140,219 | Lung adenocarcinoma | ↓ | Gan et al. 2018 |
| HOXA5 | chr7:27,141,052–27,143,681 | Cervical cancer, osteosarcoma, breast cancer, gastric cancer, non-small cell lung cancer, colorectal cancer | ↓ | Chen et al. 2004; Chen et al. 2019; Ma et al. 2020; Ordóñez-Morán et al. 2015; Peng et al. 2018; Raman et al. 2000; Wang et al. 2019c; Zhang et al. 2015 | |
| HOXD cluster | HOXD1 | chr2:176,188,668–176,190,907 | Kidney renal clear-cell carcinoma | ↓ | Cui et al. 2021 |
| HOXD8 | chr2:176,130,357–176,132,000 | Colorectal cancer | ↓ | Mansour and Senga 2017 | |
| HOXD13 | chr2:176,092,721–176,095,944 | Prostate cancer | ↓ | Xu et al. 2021 | |
| HOX genes with both oncogenic and tumor suppressor activity | |||||
| HOXA cluster | HOXA4 | chr7:27,128,507–27,130,780 | High-grade serous ovarian carcinoma | ↑ | Miller et al. 2018 |
| Lung cancer | ↓ | Cheng et al. 2018 | |||
| HOXA9 | chr7:27,162,438–27,165,537 | Acute myeloid leukemia, acute lymphoblastic leukemia, ovarian cancer | ↑ | de Bock et al. 2018; Brumatti et al. 2013; Ko et al. 2012; Zhao et al. 2015 | |
| Cervical cancer, cutaneous squamous cell carcinoma | ↓ | Alvarado-Ruiz et al. 2016; Han et al. 2019 | |||
| HOXA11 | chr7:27,181,157–27,185,232 | Laryngeal squamous cell cancer | ↑ | Li et al. 2020a | |
| Glioblastoma, breast cancer | ↓ | Se et al. 2017; Xia et al. 2017 | |||
| HOXB cluster | HOXB9 | chr17:48,621,156–48,626,358 | Breast cancer, hepatocellular carcinoma, oral squamous cell carcinoma, laryngeal squamous cell carcinoma | ↑ | Hayashida et al. 2010; Sha et al. 2015; Sun et al. 2017; Xue et al. 2017 |
| Gastric cancer | ↓ | Zhang et al. 2019 | |||
| HOXB13 | chr17:48,724,763–48,728,750 | Urinary bladder cancer, breast cancer, prostate cancer | ↑ | Kim et al. 2014; Marra et al. 2013; Shah et al. 2013 | |
| Colorectal cancer | ↓ | Jung et al. 2005 | |||
| HOXD cluster | HOXD10 | chr2:176,116,778–176,119,937 | Laryngeal squamous cell carcinoma | ↑ | de Barros E Lima Bueno et al. 2016 |
| Colon cancer, hepatocellular carcinoma, cholangiocellular carcinoma | ↓ | Guo et al. 2017; Yang et al. 2015; Yuan et al. 2019 | |||
NOTE: ↑, upregulated; ↓, downregulated