Table 1.
Association between HOX gene hypermethylation and cellular processes involved in cancer progression.
| Cancer Site | HOX Genes | Possible Roles | References |
|---|---|---|---|
| Bile duct | HOXA1, HOXA2, HOXA5, HOXA11, HOXB4, HOXD9, HOXD13 | Biomarkers for the detection of cholangiocarcinoma in tissues or serum cell-free. | [31,32,33] |
| Bladder | HOXA9 | Biomarker for the detection of bladder cancer and prediction response to cisplatin-based chemotherapy and survival. | [34,35] |
| HOXB2 | Biomarker to predict high-grade, noninvasive disease. | [36] | |
| Blood (Leukemias/ Lymphomas) | HOXA4 | Biomarker to predict resistance to imatinib mesylate. | [37] |
| HOXA4, HOXA5 | Biomarkers to predict progression to blast crisis. | [38] | |
| HOXD8 | Targeted for therapeutic benefit in MCL (Mantle cell lymphoma). | [39] | |
| Breast | HOXA1 | Biomarker to distinguish different breast cancer states subgroups. | [24,40] |
| HOXA4 | Biomarker for early breast cancer detection. | [41] | |
| HOXA5 | Biomarker specific to high-grade ductal carcinoma in situ detection and Triple-Negative breast cancer nonresponders to neoadjuvant chemotherapy. | [42,43] | |
| HOXA9, HOXA10 | Biomarkers to predict survival. | [44] | |
| HOXA10, HOXB13 | Biomarker to distinguish different breast cancer states subgroups with high expression of estrogen and progesterone receptors. | [24,40] | |
| HOXA11 | Biomarker for unfavorable prognosis in breast cancer. | [45] | |
| HOXB4 | Biomarker for metastatic breast cancer detected in circulating tumor cells. | [46] | |
| HOXB13 | Biomarkers for the detection of breast cancer. | [47] | |
| HOXC8 | Epigenetic downregulation interferes with stem cell transformation. | [48] | |
| HOXC9 | Detected in breast cancer. | [49] | |
| HOXC10 | Detected in endocrine-resistant breast cancer and associated with recurrence during aromatase inhibitor treatment. | [50] | |
| HOXD1 | Biomarkers for the detection and prognosis of breast cancer. | [51] | |
| HOXD11 | Detected in breast cancer. | [52] | |
| HOXD13 | Biomarker for poor survival prognostic. | [53] | |
| Cervix | HOXA9 | Epigenetic downregulation relates to cell proliferation, migration and expression of epithelial-to-mesenchymal transition genes. | [54] |
| Colorectal | HOXA2 | Epigenetic downregulation relates to lymphovascular invasion, perineural invasion, lymph node number. | [38] |
| HOXA5, HOXA6 | Epigenetic downregulation favors tumor progression. | [55] | |
| HOXD3 | Identified in colorectal cancers. | [56] | |
| HOXD10 | Epigenetic downregulation favors proliferation, migration, invasion and apoptosis. | [57] | |
| Endometrial | HOXA9, HOXD10 | Biomarker for detection of early onset of endometrial cancer. | [58] |
| Kidney | HOXA5 | Epigenetic downregulation associated with high-grade clear cell renal cell carcinoma. | [59] |
| HOXA11 | Epigenetic downregulation associated with proliferation, colony formation, migration and invasion abilities in renal cell carcinoma. | [60] | |
| HOXB13 | Epigenetic downregulation associated with reduced apoptosis and increased tumor grade and microvessel invasion in renal cell carcinoma. | [61] | |
| Head and neck | HOXA5 | Epigenetic downregulation favors invasion in nasopharyngeal cancer. | [62] |
| HOXB2 | Biomarker for lymph node metastasis in esophageal squamous cell carcinoma. | [63] | |
| HOXA9 | Epigenetic downregulation associated with tumor progression and metastasization in head and neck squamous cell carcinoma and biomarker to distinguish oral cancer patients at low risk of neck metastasis. | [64,65] | |
| HOXB4, HOXC4 | Biomarkers to predict survival of oral squamous cell carcinoma. | [66] | |
| Liver | HOXD10 | Epigenetic downregulation activates ERK signaling in hepatocellular carcinoma and causes vessel cancerous embolus and tumor cell differentiation. | [67] |
| HOXB4 | Epigenetic downregulation disruption of miR-10ª regulation hepatocellular carcinoma. | [68] | |
| Lung | HOXA1, HOXA11 | Biomarker involved in a molecular signature that helps to distinguish between atypical adenomatous hyperplasia, adenocarcinoma in situ and lung adenocarcinoma | [69] |
| HOXA2 | Biomarker involved in a molecular signature that helps to stratify lung squamous cell carcinoma into molecular subtypes with distinct prognoses. | [70] | |
| HOXA2, HOXA10 | Biomarkers relevant for the prognosis of nonsmall cell lung cancer patients. | [71] | |
| HOXA3 | Epigenetic downregulation in lung adenocarcinoma is associated with progression and poor prognosis. | [72] | |
| HOXA5 | Epigenetic downregulation favors tumor-node-metastasis, tumor size, and lymph node metastasis in nonsmall cell lung cancer. It also favors invasion in lung adenocarcinomas. | [73,74] | |
| HOXA5, HOXA10, HOXA4, HOXA7, HOXD13 | Identified in lung cancer. | [75] | |
| HOXA7, HOXA9 | Epigenetic downregulation is associated with recurrence in nonsmall cell lung cancer. This alteration is part of a molecular signature relevant for detection and prognostic of primary nonsmall cell lung cancer using serum DNA. | [76,77] | |
| HOXA11 | Epigenetic downregulation is associated with progression of nonsmall cell lung cancer. This alteration is part of a molecular signature involved in cell proliferation and migration in lung adenocarcinoma. | [78,79] | |
| HOXB3, HOXB4 | Biomarkers in lung adenocarcinomas correlated with smoking history and chronic obstructive pulmonary disease. | [80] | |
| HOXD3 | Biomarker for lung cancer. | [56] | |
| HOXD8 | Epigenetic downregulation correlated with clinicopathological characteristics, cell migration and metastasization | [81] | |
| HOXD10 | Biomarker to distinguish lung cancer, pulmonary fibrosis and chronic obstructive lung disease. | [82] | |
| HOXD13 | Biomarker for lung adenocarcinoma. | [83] | |
| Nervous System | HOXA3, HOXA7, HOXA9, HOXA10 | Biomarkers to distinguish different glioma subgroups. | [84] |
| HOXA10 | Part of a stem cell related HOX-signature in glioblastoma. | [85] | |
| HOXA11 | Epigenetic downregulation associated with treatment resistance and poor prognosis in glioblastoma. | [86] | |
| HOXC4, HOXD8, HOXD13 | Biomarkers that distinguish long- and short-term glioblastoma survivors. | [87] | |
| Ovaries | HOXA9, HOXD11 | Epigenetic downregulation involved in DNA repair inactivation, cell cycle, apoptosis, cell adherence in ovarian cancer | [88] |
| HOXA9, HOXB5 | Identified in ovarian cancer and correlated with clinicopathological characteristics. | [89] | |
| HOXA10, HOXA11 | Prognostic biomarker in ovarian cancer. | [90] | |
| Prostate | HOXA9 | Part of a molecular signature for prostate cancer clinical staging based on urine collection. | [91] |
| HOXD3 | Identified in prostate cancer and related to the development of high-grade tumors and recurrence | [92,93] | |
| HOXD8 | Urine-based methylation biomarkers to predict prostate cancer progression. | [94] | |
| Stomach | HOXA1, HOXA10, HOXD10 | Biomarker for the diagnosis of gastric cancer. | [95] |
| HOXA10 | Interferes with miR-196b-5p-dependent proliferation and invasion of gastric cancer cells. | [30] | |
| HOXA11 | Identified in gastric cancer and proposed to affect cell proliferation. | [96] | |
| HOXB13 | Biomarker for gastric cancer involved in invasion depth, lymph node metastasis and tumor-node-metastasis stage. | [97] | |
| HOXD1 | Biomarkers for predicting lymph node metastasis of stomach cancer. | [98] | |
| HOXD10 | Epigenetic downregulation associated with gastric carcinogenesis. | [99] | |
| Testis | HOXA9 | Biomarker for testicular germ cell tumor subtyping. | [100] |
| Thyroid | HOXA1 | Biomarker for the diagnosis of thyroid nodules. | [101] |
| HOXA7 | Biomarker for papillary thyroid cancer. | [102] | |
| HOXB4 | Part of a molecular signature identifying biologically distinct thyroid cancer subtypes. | [103] | |
| HOXD10 | Identified in papillary thyroid cancer with BRAFV600E mutation and associated with primary tumor invasion and age > 45. | [104] |