To provide more insight into the mechanistic underlining and pathobiological implication of the differential but concerted alteration of the HSD17B2, HSD17B3, SHBG, and SRD5A1 testosterone tetrad in disease course and therapy response of patients with PCa, we further probed the discovery cohort of the GSE70768 dataset (n = 199), consisting of complete, quality-controlled HT12v4 data for 13 castration-resistant prostate cancer (CRPC), 113 tumor, and 73 matched benign samples. Here, HSD17B3 is linked to neoplasm.