Down-regulation of RB1 and TP53 as potential predicting biomarkers for castration-resistant prostate cancer (CRPC): Indonesian retrospective cohort study

Introduction: Androgen deprivation therapy (ADT) has remained the first line strategy for treatment of advanced prostate cancers. Despite the profound efficacy of ADT in preventing clinical remission, 30-50% of advanced prostate cancer will develop resistance to hormonal deprivation therapy. This study aimed to evaluate the potential role of RB1 and TP53 expressions as biomarkers for predicting time to castration-resistant prostate cancer (CRPC). Methods: The clinical and pathological data of patients with prostate cancer were collected retrospectively from Dr. Sardjito General Hospital, Yogyakarta. Between 2015 and 2019, a total of 36 patients who received castration were included. Expressions of mRNA of RB1 and TP53 from primary tumors were quantified using quantitative Real Time Polymerase Chain Reaction (qRT-PCR). Results: The expressions of mRNA of RB1 and TP53 increased in prostate cancer tissues compared to hyperplastic prostates and significantly downregulated in metastatic prostate cancers (p < 0.001). Lower mRNA TP53 expression correlated with shorter time to CRPC among patients treated with ADT (p = 0.006). In addition, stratified analysis showed that lower mRNA RB1 expression was significantly associated with shorter CRPC both in metastatic (p = 0.017) and non-metastatic (p = 0.001) prostate cancer patients. Conclusions: Low expression of mRNA of RB1 and TP53 has been shown to be a potential marker of shorter time to develop CRPC in patients with advanced stages of prostate cancer treated with ADT. Meanwhile, ISUP score >4 were not shown predictive value on time to CRPC.