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Positive expression of NR6A1/CT150 as a predictor of biochemical recurrence-free survival in prostate cancer patients.

ABSTRACT: NR6A1/CT150, as an orphan receptor, is a novel member of the cancer-testis (CT) antigen family. Here, we investigated the expression and function of NR6A1 and its underlying mechanisms in prostate cancer (PCa) patients who underwent radical prostatectomy. A total of 303 cases of prostate cancer after radical prostatectomy were analysed in a tissue microarray (TMA) for NR6A1 immunohistochemistry-based protein expression. Kaplan-Meier/log-rank analysis and Cox regression analysis were used to investigate the relationship between NR6A1 expression and clinicopathological factors in PCa. NR6A1 mRNA expression was examined by reversing transcriptase-polymerase chain reaction (RT-PCR). Knockdown of NR6A1 by small interfering RNA mediated gene silencing and overexpression of NR6A1 through lentivirus were utilized to investigate its potential role in prostate cancer cells. NR6A1 protein expression was 29.7% (90/303) and mRNA expression was 28.1%(9/32) in PCa patients. NR6A1 expression was significantly associated with Gleason score (GS) (P=0.003) and tumor stage (P=0.042). The patients with positive NR6A1 expression have a shorter biochemical recurrence-free survival. NR6A1 predicted biochemical recurrence in univariate (P=0.0159) and multivariate models (P=0.0317). In addition, gene silencing of NR6A1 resulted in G0/G1 phase cell cycle arrest, and decreased metastatic and invasive potential of prostate cancer cells DU145 and PC3. In contrast, overexpression of NR6A1 reduced G0/G1 phase cell cycle arrest, and promoted metastatic and invasive potential of prostate cancer cells 22RV1. And overexpression of NR6A1 significantly promoted tumor growth in vivo. What's more, down regulation of NR6A1 could reverse epithelial-to-mesenchymal transition (EMT) process in DU145 and PC3 cell lines, and the overexpression could enhance EMT process in 22RV1 cell line. NR6A1 played a prominent role in migration and invasion of PCa cells, and it is indicated that NR6A1 may act as a novel marker for biochemical recurrence after radical prostatectomy.

SUBMITTER: Cheng G

PROVIDER: S-EPMC5610014 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Positive expression of NR6A1/CT150 as a predictor of biochemical recurrence-free survival in prostate cancer patients.

Cheng Gong G Wang Shangqian S Li Xiao X Li Shuang S Zheng Yang Y Zhang Lei L Bao Meiling M Liang Chao C Huang Zhengkai Z Liu Yiyang Y Qin Chao C Shao Pengfei P Li Jie J Hua Lixin L Yin Changjun C Wang Zengjun Z

Oncotarget 20160831 38

NR6A1/CT150, as an orphan receptor, is a novel member of the cancer-testis (CT) antigen family. Here, we investigated the expression and function of NR6A1 and its underlying mechanisms in prostate cancer (PCa) patients who underwent radical prostatectomy. A total of 303 cases of prostate cancer after radical prostatectomy were analysed in a tissue microarray (TMA) for NR6A1 immunohistochemistry-based protein expression. Kaplan-Meier/log-rank analysis and Cox regression analysis were used to inve ...[more]

PMID: 28969082

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Project description:BackgroundBiochemical recurrence (BCR) after initial treatment, such as radical prostatectomy, is the most frequently adopted prognostic factor for patients who suffer from prostate cancer (PCa). In this study, we aimed to construct a prognostic model consisting of gene expression profiles to predict BCR-free survival.MethodsWe analyzed 70 metabolic pathways in 152 normal prostate samples and 494 PCa samples from the UCSC Xena dataset (training set) via gene set enrichment analysis (GSEA) to select BCR-related genes and constructed a BCR-related gene risk score (RS) model. We tested the power of our model using Kaplan-Meier (K-M) plots and receiver operator characteristic (ROC) curves. We performed univariate and multivariate analyses of RS using other clinicopathological features and established a nomogram model, which has stronger prediction ability. We used GSE70770 and DFKZ 2018 datasets to validate the results. Finally, we performed differential expression and quantitative real-time polymerase chain reaction analyses of the UCSC data for further verification of the findings.ResultsA total of 194 core enriched genes were obtained through GSEA, among which 16 BCR-related genes were selected and a three-gene RS model based on the expression levels of CA14, LRAT, and MGAT5B was constructed. The outcomes of the K-M plots and ROC curves verified the accuracy of the RS model. We identified the Gleason score, pathologic T stage, and RS model as independent predictors through univariate and multivariate Cox analyses and constructed a nomogram model that presented better predictability than the RS model. The outcomes of the validation set were consistent with those of the training set. Finally, the results of differential expression analyses support the effectiveness of our model.ConclusionWe constructed an RS model based on metabolic genes that could predict the prognosis of PCa patients. The model can be easily used in clinical applications and provide important insights into future research on the underlying mechanism of PCa.

Project description:PurposeThere have been conflicting reports regarding the association of perioperative blood transfusion (PBT) with oncologic outcomes including recurrence rates and survival outcomes in prostate cancer. We aimed to evaluate whether perioperative blood transfusion (PBT) affects biochemical recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS) following radical prostatectomy (RP) for patients with prostate cancer.Materials and methodsA total of 2,713 patients who underwent RP for clinically localized prostate cancer between 1993 and 2014 were retrospectively analyzed. We performed a comparative analysis based on receipt of transfusion (PBT group vs. no-PBT group) and transfusion type (autologous PBT vs. allogeneic PBT). Univariate and multivariate Cox-proportional hazard regression analysis were performed to evaluate variables associated with BRFS, CSS, and OS. The Kaplan-Meier method was used to calculate survival estimates for BRFS, CSS, and OS, and log-rank test was used to conduct comparisons between the groups.ResultsThe number of patients who received PBT was 440 (16.5%). Among these patients, 350 (79.5%) received allogeneic transfusion and the other 90 (20.5%) received autologous transfusion. In a multivariate analysis, allogeneic PBT was found to be statistically significant predictors of BRFS, CSS, and OS; conversely, autologous PBT was not. The Kaplan-Meier survival analysis showed significantly decreased 5-year BRFS (79.2% vs. 70.1%, log-rank, p = 0.001), CSS (98.5% vs. 96.7%, log-rank, p = 0.012), and OS (95.5% vs. 90.6%, log-rank, p < 0.001) in the allogeneic PBT group compared to the no-allogeneic PBT group. In the autologous PBT group, however, none of these were statistically significant compared to the no-autologous PBT group.ConclusionsWe found that allogeneic PBT was significantly associated with decreased BRFS, CSS, and OS. This provides further support for the immunomodulation hypothesis for allogeneic PBT.

Project description:Background: D'Amico high-risk prostate cancer (Pca) patients experience poor and heterogeneous oncological outcomes. This heterogeneity highlights a need to extensively explore factors associated with poor outcomes to guide decision-making. Objective: To assess predictors of biochemical recurrence (BCR)-free survival in high-risk patients following radical prostatectomy (RP), and subsequently establish a model predicting outcomes. Methods: We retrospectively identified D'Amico high-risk non-metastatic Pca patients who underwent RP between 2013 and 2019 in our hospital. We collected data including PSA level, clinical stage, biopsy Gleason score (GS), number of D'Amico high-risk factors (RF), the inflammatory status (Neutrophil-to-lymphocyte ratio [NLR], derived NLR [dNLR], platelet-to-lymphocyte ratio [PLR] and LDH). Kaplan–Meier methods were used to analyze BCR-free survival. Univariate and multivariate analyses were performed using Cox proportional hazards model to evaluate the association between clinicopathological parameters and BCR-free survival. Results: The median follow-up time for the 101 patients' cohort was 26 months (range: 3–81 months). The number of RF (1RF vs. ?2RF), biopsy GS (<8 vs. ?8), clinical stage (?cT2c vs. >cT2c), pathological stage, and the presence of adverse pathological features were significant predictors of BCR (P < 0.05). Other parameters including inflammatory status (dNLR, NLR, PLR, and LDH) were not of predictive value. On multivariable analysis, biopsy GS (<8 vs. ?8; HR 2.439) and clinical stage (?cT2c vs. >cT2c; HR 3.271) were the independent predictors of BCR. Based on these two independent predictors, patients were stratified into three risk subgroups: favorable (0 risk factor; 47% of patients), intermediate (1 risk factor; 42 %), unfavorable (2 risk factors; 11%). The intermediate and unfavorable subgroups have a significantly shorter median BCR-free survival compared to the favorable subgroup (P < 0.001). Conclusion: Several factors are associated with BCR. Clinical stage (?cT2c vs. >cT2c) and biopsy GS (<8 vs. ?8) are the independent predictors of BCR. The stratification of high-risk patients into risk subgroups based on these two predictors shows that the intermediate and unfavorable subgroups have a significantly shorter median BCR-free survival compared to the favorable subgroup. The preoperative stratification model may help urologists and patients during decision-making. In non-metastatic high-risk patients, preoperative inflammatory markers (NLR, dNLR, PLR, and LDH) are not of prognostic value.

Dataset Information

Positive expression of NR6A1/CT150 as a predictor of biochemical recurrence-free survival in prostate cancer patients.

Publications

Positive expression of NR6A1/CT150 as a predictor of biochemical recurrence-free survival in prostate cancer patients.

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