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

Abstract

IntroductionAndrogen 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). MethodsThe 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). ResultsThe 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. ConclusionsLow 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.