For a study, researchers sought to look at a variety of strategies to quantify AR-V7 mRNA and protein in prostate cancer cell lines, patient-derived xenograft (PDX) models, publicly available cohorts, and independent institutional clinical cohorts to discover effective techniques for detecting AR-V7 mRNA and protein and its correlation with clinical outcome. In castration-resistant prostate cancer (CRPC), expression of the constitutively active androgen receptor (AR) splice variant-7 (AR-V7) has demonstrated clinical usefulness as a biomarker of AR-targeted therapy resistance, but its significance in castration-sensitive prostate cancer (CSPC) was yet unknown. When compared to isoform-specific exonic readings that span splice boundaries, the CSPC and CRPC groups significantly reduced AR-V7 mRNA abundance. When compared to the EPR15656 AR-V7 antibody, the RM7 AR-V7 antibody demonstrated improved sensitivity and specificity for AR-V7 protein detection by immunohistochemistry (IHC) in CRPC cohorts but infrequently detected AR-V7 protein reactivity in CSPC cohorts. They showed that the expression of AR-V7 was highly sensitive to hormone therapy using a number of CRPC PDX models. In CSPC institutional cohorts, there was no correlation between the development of castration resistance or overall survival and the quantification of AR-V7 protein by either test, and intensive neoadjuvant androgen-deprivation therapy did not result in any detectable AR-V7 mRNA or staining after treatment. In addition, the degree of illness that persisted after treatment did not correlate with pre- or post-treatment AR-V7 levels. This study showed that additional clinical certification and analytical validation were required before AR-V7 may be used as a prognostic biomarker in CSPC.
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