Abstract
BackgroundWe aimed to establish a novel epithelial-mesenchymal transition (EMT)-related gene prognostic index (EMTGPI) associated with biochemical recurrence (BCR) and drug resistance for prostate cancer (PCa).MethodsWe used Lasso and Cox regression analysis to establish the EMTGPI. All analyses were conducted with R version 3.6.3 and its suitable packages.ResultsWe established the EMTGPI based on SFRP4 and SPP1. Patients in high-risk group had 2.23 times of BCR risk than those in low-risk group (p = 0.003), as well as 2.36 times of metastasis risk (p = 0.053). In external validation, we detected similar diagnostic efficacy and prognostic value in terms of BCR free survival. For drug resistance, we observe moderately diagnostic accuracy of EMTGPI score (AUC: 0.804). We found that PDCD1LG2 (p = 0.04) and CD96 (p = 0.01) expressed higher in BCR patients compared with their counterpart. For TME analysis, we detected that CD8+ T cells and M1 macrophages expressed higher in BCR group. Moreover, stromal score (p = 0.003), immune score (p = 0.01), and estimate score (p = 0.003) were higher in BCR patients. We found that EMTGPI was significantly related to HAVCR2 (r: 0.34), CD96 (r: 0.26), CD47 (r: 0.22), KIR3DL1 (r: −0.21), KLRD1 (r: −0.21), and CD2 (r: 0.21). In addition, we observed that EMTGPI was significantly associated with M1 macrophages (r: 0.6), M2 macrophages (r: −0.33), monocytes (r: −0.18), neutrophils (r: −0.43), CD8+ T cells (r: 0.13), and dendritic cells (r: 0.37). PHA-793887 was the common drug sensitive to SPP1 and SFRP4, and PC3 and DU145 were the common PCa-related cell lines of SPP1, SFRP4, and PHA-793887.ConclusionsWe concluded that the EMTGPI score based on SFRP4 and SPP1 could be used to predict BCR for PCa patients. We confirmed the impact of immune evasion on the BCR process of PCa.
Highlights
It is known that metastatic castration-resistant Prostate cancer (PCa) (MCRPC) is the leading cause of cancer death with an estimated mortality rate of almost 28% for 5-year survival [5]
We identified 13 candidate genes, and SFRP4 and SPP1 were used to construct the EMT-related gene prognostic index (EMTGPI) after LASSO and Cox regression analyses (Figures 2A–E)
According to the median of EMTGPI score based on SFRP4 and SPP1, we divided the 248 patients undergoing radical radiotherapy in GSE116918 [19] into highand low-risk groups
Summary
Aging population has already been a social dilemma worldwide and accounts for almost 20.8% of the population by 2044 [1]. Prostate cancer (PCa), one of the most common age-related diseases, ranks the second most frequent cancer and the fifth leading cause of cancer death in men in 2020 [2]. PCa often suffers from drug resistance and progress to castration-resistant state despite using new potent antiandrogen drugs, like abiraterone and enzalutamide [3, 4]. It is known that metastatic castration-resistant PCa (MCRPC) is the leading cause of cancer death with an estimated mortality rate of almost 28% for 5-year survival [5]. There has been much division between urologists on the molecular mechanism of metastasis and tumor chemoresistance in PCa. We aimed to establish a novel epithelial-mesenchymal transition (EMT)related gene prognostic index (EMTGPI) associated with biochemical recurrence (BCR) and drug resistance for prostate cancer (PCa)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
