Importance of HOX genes in normal prostate gland formation, prostate cancer development and its early detection

Abstract

• The aims of this paper were to review the published literature on the role of HOX genes in the development of the normal prostate gland and in prostate cancer and to discuss the potential role of the HOX family member, Engrailed-2 (EN2), as a diagnostic test of PCa.• Hox genes were first described in the fruit fly Drosphila melanogaster, where they specify the body plan and control the formation of body segments. They belong to a family of homeodomain-containing transcription factors that determine cell and tissue identity during normal embryonic development. They have been shown to be re-expressed by several different types of cancers. • Studies have shown that different Hox genes are responsible for the development of the separate lobes of the prostate gland, the seminal vesicles and the epididymis. All HOX13 paralogues are expressed in the adult human prostate, suggesting the possibility of similarities between the function and expression of HOX genes within urological structures at similar anterior-posterior positions.• The oncogenic and tumour suppressor signalling pathways associated with PCa converge on the HOX gene network, which ultimately controls gene expression, affecting tumour formation and metastatic progression.• The Engrailed genes (EN1 and EN2) from the HOX gene family show a very high degree of functional conservation during embryonic development.• Urinary EN2 is being investigated as a potential diagnostic marker of early PCa. It is secreted into the urine by PCa cells but not by normal prostatic tissue. A recent study has shown an association between urinary EN2 levels and cancer volume in radical prostatectomy specimens. The ability to predict tumour volume could inform the treatment decision-making process for patients with localized PCa choosing between active surveillance and radical treatment options.

PBX3 is a putative biomarker of aggressive prostate cancer

“…HOX genes are developmental genes shown to be master regulatory transcription factors involved in embryogenesis . A number of HOX genes are essential in the development of the prostate gland and their expression pattern is altered in prostate cancer . A genomic pathway analysis has showed that loss of the HOXA9 co‐factors PBX1 , MEIS1 and MEIS2 are associated with prostate tumorigenesis and progression .…”

SpidermiR: An R/Bioconductor Package for Integrative Analysis with miRNA Data

“…The HOX gene family includes various transcription factors that help to determine cell and tissue identity in the early development of PC [35], and increase greatly during the development of PC [36]. …”

“…In addition several members of the HOX family (e.g., HOXB6 , B7 ) that belong to this subnetwork, are involved in PC onset [35] or development [36]. …”

DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy

“…It is a heterogeneous disease with regard to clinical course and molecular alterations (Al-Maghrebi et al , 2012). The tests used in clinical practice to diagnose PCa, including the measurement of serum PSA, DRE and TRUS-guided biopsies, have significant limitations (Javed and Langley, 2013). More than 60% of biopsies conducted based on PSA test results ultimately turn up negative (Altintas et al , 2013).…”