International Journal of Clinical Case Reports 2024, Vol.14, No.4, 202-209 http://medscipublisher.com/index.php/ijccr 204 Figure 1 A schematic showing key mitotic kinases over-expressed in metastatic PCs and regulated by HOXB13. HSPB8 functions as a restraint against PC metastasis (Adopted from Yao et al., 2019). 3.2 Interaction betweenHOXB13 and androgen receptor signaling pathways HOXB13 interacts closely with the androgen receptor (AR), which is critical for prostate cancer progression. In castration-resistant prostate cancer (CRPC), HOXB13 acts as a co-regulator of AR and its splice variant AR-V7, facilitating ligand-independent AR-driven transcriptional activity (Song et al., 2024). This interaction has been linked to the development of resistance to androgen deprivation therapy (ADT) and is associated with poor prognosis in prostate cancer patients. HOXB13 enhances the expression of AR target genes involved in cell survival and proliferation, thus promoting tumor growth even in the absence of androgens (Coutinho et al., 2016; Chen et al., 2018). Additionally, HOXB13 cooperates with other co-regulators like FOXA1 and GATA2 to activate AR signaling, which contributes to the metastatic potential of prostate cancer (Hankey et al., 2020). 3.3 Relationship betweenHOXB13 gene variants and prostate cancer metastasis and progression HOXB13 expression is significantly associated with increased prostate cancer metastasis and disease progression. High levels of HOXB13 have been correlated with advanced tumor stages and poor clinical outcomes following radical prostatectomy. In particular, HOXB13 promotes metastasis through the regulation of bone metastasis-related genes, such as those involved in cytokine signaling and integrin-mediated adhesion, which enhance the ability of cancer cells to invade bone tissue. Studies have shown that the HOXB13-HOXA11-AS axis modulates bone metastasis by regulating critical genes like CCL2/CCR2 and IBSP, which are involved in cell invasion and the formation of metastatic lesions (Misawa et al., 2021). Moreover, HOXB13 interacts with AR-V7 to drive prostate cancer cell migration and metastasis, particularly in castration-resistant cases, by maintaining chromatin accessibility at AR-binding sites that promote aggressive cancer phenotypes (Sharp et al., 2018). 4 Clinical Applications and Predictive Value 4.1 HOXB13 gene variants as early diagnostic markers for prostate cancer The HOXB13 G84E mutation has emerged as a promising biomarker for early detection of prostate cancer, especially in men with a family history of the disease. Several studies have demonstrated that men carrying the G84E variant have a significantly increased risk of developing prostate cancer, particularly at an early age.
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==