Table 1.

Signatures involving TF biology in PCa. There have been significant advances in molecularly subtyping PCa with a few diagnostic and prognostic tests available [33]. However, the widespread clinical utility of such tests in PCa is still being reviewed, with the complex underlying biology and disease heterogeneity posing significant barriers to a population-wide utilization. Moreover, most commercially available signatures were the products of reverse translation and clinical profiling. This is because the application of these signatures is in an incredibly complex setting (the clinic), and so far, there have not been sufficiently powerful pre-clinical models to overcome issues such as heterogeneity. This is increasingly being addressed by the emergence of patient-derived explants and organoids, which offer a significantly improved translational model of PCa compared to cell lines. As this table demonstrates, there is a drive in pre-clinical research to combine signatures to determine the effect of multiple key molecular pathways on disease evolution. This is a space that most commercially available signatures are currently not occupying as they focus on singular TFs (androgen receptor; AR) or single biologies (cell cycle progression; CCP). The further commercial and clinical validation of such approaches is of course needed, and this will be aided by the development of academic–government–industry collaborations and extensive biobank-databank repositories. MITF: microphthalmia-associated transcription factor; CPRC: castration-resistant prostate cancer.

Scheme	Signature	Mechanism	Translation	Ref.
Commercial	Oncotype DX	12 genes related to androgen metabolism, cellular organization, proliferation, and stromal response plus 5 reference genes	Reverse	[34,35]
	Prolaris	31 cell cycle genes	Reverse	[36]
	Decipher	22 genes involved in proliferation, structure, immune modulation, cell cycle and androgen signaling	Reverse	[37]
	ExoDX	Urinary-derived exosomal gene signature based on PCA3 and ERG RNA levels	Reverse	[38]
	SelectMDx	2 gene signature (DLX1 and HOXC6)	Reverse	[39]
Academic	Hypoxia-28	6 hypoxia and 11 PCa signature overlap	Combinatorial	[40]
	BROMO-10	10 gene signature from bromodomain inhibitor treated cells and PCa cohorts	Forward	[41]
	AR-v7	Variant correlation with 59 gene CRPC signature	Reverse	[42]
	SIG-DENT SIG-HES6	Overlapping PCa-related signatures	Combinatorial	[43]
	Primary PCa metastatic assay	70 gene signature to predict risk of biochemical recurrence	Reverse	[44]
	AR–MITF–Myc	Combination of signatures to prognosticate PCa survival	Forward	[45,46]
	MycN-EZH2	Transcriptome/cistrome/interactome N-Myc-derived signature in advanced PCa	Forward	[47]
	mCRPC-26	Treatment-resistant CRPC classification	Combinatorial	[48]