Evaluation of PUMA and NOXA expression as predictive biomarkers in prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 28-28
Author(s):  
Sylvie Clairefond ◽  
Benjamin Péant ◽  
Veronique Ouellet ◽  
Veronique Barres ◽  
Anne-Marie Mes-Masson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Tumor Tissue ◽  
Prostate Cancer Cell ◽  
Cox Regression ◽  
Predictive Biomarkers ◽  
Tissue Microarrays ◽  
Kaplan Meier ◽  
Puma Expression ◽  
Risk Patients

28 Background: PUMA and NOXA are two pro-apoptotic members of the BH3-only subgroup of the BCL-2 family. These two proteins play a role in the initiation of apoptosis. The objective of this study is to analyse their expression by immunofluorescence, alone or in combination, in benign and tumor prostate tissues to determine if there is a correlation between their expression and patient biochemical recurrence (BCR). Methods: Biomarker antibodies were verified for specificity and optimized by western blot and with tissue microarrays (TMA) containing prostate cancer cell lines and cell line derived xenograft tissues. Subsequently, quantification of expression for both biomarkers was performed on six TMA generated from radical prostatectomy samples (285 patients). The TMA were constructed using two cores of benign adjacent to the tumor and two cores of tumor tissue from each patient. Analysis of biomarker expression was semi-automated using the VisiomorphDP software. To optimize the analysis, we developed 2 different immunofluorescence masks: a cocktail of anti-cytokeratin-8 and -18 antibodies to identify epithelial cells and a combination of anti-p63 and anti-cytokeratin high marker weight to discriminate benign glands within tumor cores. Correlation with patient clinical outcome was determined with SPSS V20 software. Results: There was no correlation of PUMA and NOXA expression and BCR in tumor cores and stroma. In contrast, in benign epithelial cells Kaplan-Meier analysis showed a significant association between an extreme (low or high) PUMA expression and BCR (Log rank = 11.349, p = 0.001). Further analysis revealed a significant association between high NOXA expression in benign epithelial cells and BCR (Log rank = 6.133, p = 0.013). The combination of extreme PUMA and high NOXA identified patients with a poor prognosis (Log rank = 16.041, p = 0.000). In a multivariate Cox regression model, PUMA and NOXA proteins were also identified as independent predictive biomarkers of BCR. Conclusions: By studying benign epithelial cells adjacent to the tumor we identified two potential biomarkers that discriminate high-risk patients, independent of Gleason score or pathologic stage.

scholarly journals PUMA and NOXA Expression in Tumor-Associated Benign Prostatic Epithelial Cells Are Predictive of Prostate Cancer Biochemical Recurrence

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3187
Author(s):  
Sylvie Clairefond ◽  
Benjamin Péant ◽  
Véronique Ouellet ◽  
Véronique Barrès ◽  
Zhe Tian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Epithelial Cells ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Regression Analyses ◽  
Kaplan Meier ◽  
Puma Expression

Background: Given that treatment decisions in prostate cancer (PC) are often based on risk, there remains a need to find clinically relevant prognostic biomarkers to stratify PC patients. We evaluated PUMA and NOXA expression in benign and tumor regions of the prostate using immunofluorescence techniques and determined their prognostic significance in PC. Methods: PUMA and NOXA expression levels were quantified on six tissue microarrays (TMAs) generated from radical prostatectomy samples (n = 285). TMAs were constructed using two cores of benign tissue and two cores of tumor tissue from each patient. Association between biomarker expression and biochemical recurrence (BCR) at 3 years was established using log-rank (LR) and multivariate Cox regression analyses. Results: Kaplan–Meier analysis showed a significant association between BCR and extreme levels (low or high) of PUMA expression in benign epithelial cells (LR = 8.831, p = 0.003). Further analysis revealed a significant association between high NOXA expression in benign epithelial cells and BCR (LR = 14.854, p < 0.001). The combination of extreme PUMA and high NOXA expression identified patients with the highest risk of BCR (LR = 16.778, p < 0.001) in Kaplan–Meier and in a multivariate Cox regression analyses (HR: 2.935 (1.645–5.236), p < 0.001). Conclusions: The combination of PUMA and NOXA protein expression in benign epithelial cells was predictive of recurrence following radical prostatectomy and was independent of PSA at diagnosis, Gleason score and pathologic stage.

scholarly journals CCBE1 is a Prognostic Biomarker and Contributes to Prostate Cancer Cell Progression.

2021 ◽  
Author(s):  
Peizhang Li ◽  
Huan Xu ◽  
Ming Zhan ◽  
Yanbo Chen ◽  
Dachao Zheng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regression Analysis ◽  
Confidence Interval ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Cancer Tissue ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract Subject: Collagen And Calcium Binding EGF Domains 1 (CCBE1) is a coding protein which plays a significant role in extracellular matrix remodeling and migration and is involved in the development of Hennekam syndrome and lymphangiogenesis. Here, we investigate its prognostic value in prostate cancer based on TCGA database and its antioncogenic role in prostate cancer.Methods: Wilcoxon rank sum test, Pearson χ2 test, and logistic regression analysis were utilized to evaluate the correlation between CCBE1 and clinicopathological variables. Kaplan-Meier and Cox regression analysis were used to reveal the relation between CCBE1 and survival rates. The role of CCBE1 in prostate cancer was investigated using CCK-8 assay, EdU assay, and transwell experiments, respectively.Results: Here, we found that CCBE1 expression is down-regulated in prostate cancer tissue dramatically in TCGA database. Furthermore, high CCBE1 expression predicted a good prognosis in patients with prostate cancer. High expression level of CCBE1 in PRAD cohort was prominently correlated with T classification (OR =0.49 for T3&T4 vs T2, P<0.001), Gleason score (OR = 0.42 for8&9&10 vs. 6&7, P<0.001). Kaplan-Meier and Cox regression analysis showed that prostate cancer patients with high CCBE1 expression had a better progression-free interval (hazard ratio [HR]:0.50; 95% confidence interval [CI]: 0.33-0.77; P = 0.002) and overall survival (hazard ratio [HR]:0.38; 95% confidence interval [CI]: 0.15-0.92; P = 0.032). In vitro experiments indicated that overexpressed CCBE1 inhibited prostate cancer cell proliferation, migration, and invasion.Conclusion: CCBE1 plays a pivotal role in the progression of prostate cancer and up-regulated CCBE1 expression inhibits prostate cancer tumorgenicity.

Down-regulation of miR-219-5p increase the risk of cancer-related mortality in patients with prostate cancer

2021 ◽  
pp. postgradmedj-2021-139981
Author(s):  
Shimin Tang ◽  
Hao Jiang ◽  
Zhijun Cao ◽  
Qiang Zhou
Keyword(s):  
Prostate Cancer ◽  
Prediction Model ◽  
Cancer Patients ◽  
Cox Regression ◽  
Cox Model ◽  
Risk Of Death ◽  
Kaplan Meier ◽  
Risk Of Progression ◽  
Patient Prognosis ◽  
Risk Of Cancer

IntroductionProstate cancer is a common malignancy in men that is difficult to treat and carries a high risk of death. miR-219-5p is expressed in reduced amounts in many malignancies. However, the prognostic value of miR-219-5p for patients with prostate cancer remains unclear.MethodsWe retrospectively analysed data from 213 prostate cancer patients from 10 June 2012 to 9 May 2015. Overall survival was assessed by Kaplan-Meier analysis and Cox regression models. Besides, a prediction model was constructed, and calibration curves evaluated the model’s accuracy.ResultsOf the 213 patients, a total of 72 (33.8%) died and the median survival time was 60.0 months. We found by multifactorial analysis that miR-219-5p deficiency increased the risk of death by nearly fourfold (HR: 3.86, 95% CI): 2.01 to 7.44, p<0.001) and the risk of progression by twofold (HR: 2.79, 95% CI: 1.68 to 4.64, p<0.001). To quantify each covariate’s weight on prognosis, we screened variables by cox model to construct a predictive model. The Nomogram showed excellent accuracy in estimating death’s risk, with a corrected C-index of 0.778.ConclusionsmiR-219-5p can be used as a biomarker to predict death risk in prostate cancer patients. The mortality risk prediction model constructed based on miR-219-5p has good consistency and validity in assessing patient prognosis.

Differential expression of neutral endopeptidase-24.11 (neprilysin) and endothelin-converting enzyme in human prostate cancer cell lines

2002 ◽  
Vol 103 (s2002) ◽  
pp. 314S-317S ◽  
Author(s):  
Badar A. USMANI ◽  
Ben HARDEN ◽  
Norman J. MAITLAND ◽  
Anthony J. TURNER
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Prostate Cancer Cell ◽  
Neutral Endopeptidase ◽  
Prostatic Hyperplasia ◽  
Converting Enzyme ◽  
Prostate Cancer Cell Lines ◽  
Endothelin Converting Enzyme ◽  
Androgen Independent

Neutral endopeptidase-24.11 (neprilysin; NEP/CD10) is a cell surface metallopeptidase expressed by prostatic epithelial cells that degrades various bioactive peptides including endothelin. Endothelin-converting enzyme (ECE), the key enzyme of endothelin biosynthesis, catalyses the final processing step in the pathway. Neuropeptide substrates of NEP, including endothelin, have been implicated in the growth of androgen-independent prostate cancer. We have surveyed the expression of NEP and ECE in a range of prostate cancer cell lines. Western analysis reveals that ECE-1 is expressed abundantly in all the malignant cell lines tested, except for LNCaP. In contrast, LNCaP cells express high levels of NEP, while NEP was not detected in PC-3, DU145 and other metastatic cell lines that were tested. Of the normal immortalized prostate epithelial cell lines, PNT1a shows equivalent amounts of NEP and ECE. PNT2-C2 shows poor NEP expression but an abundance of ECE. P4E6, by comparison, has low levels of both ECE and NEP. These differences in expression may render these cell lines useful in experimental models for future study. Benign prostatic hyperplasia primary epithelial cells express much higher levels of NEP than malignant primary epithelial cells, but neither show ECE expression. On the other hand, surrounding stromal cell populations have detectable ECE levels. An absence of ECE in malignant and benign prostatic hyperplasia cells of primary epithelial origin suggests an important role for stromal interaction and paracrine production of ECE within the host. The upregulation of ECE expression in metastatic cells in culture may be indicative of its role in metastatic progression. A differential profile of ECE and NEP could contribute to an abundance of mitogenic peptides aiding the progression of androgen-independent prostate cancer.

scholarly journals Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Necrosis Factor Receptor ◽  
Tissue Microarrays ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

scholarly journals Identification of a Ubiquitin Related Genes Signature for Predicting Prognosis of Prostate Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Guoda Song ◽  
Yucong Zhang ◽  
Hao Li ◽  
Zhuo Liu ◽  
Wen Song ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Roc Curve ◽  
Cox Regression ◽  
R Package ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Post Translational Modifications ◽  
Training Cohort ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Background: Ubiquitin and ubiquitin-like (UB/UBL) conjugations are one of the most important post-translational modifications and involve in the occurrence of cancers. However, the biological function and clinical significance of ubiquitin related genes (URGs) in prostate cancer (PCa) are still unclear.Methods: The transcriptome data and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA), which was served as training cohort. The GSE21034 dataset was used to validate. The two datasets were removed batch effects and normalized using the “sva” R package. Univariate Cox, LASSO Cox, and multivariate Cox regression were performed to identify a URGs prognostic signature. Then Kaplan-Meier curve and receiver operating characteristic (ROC) curve analyses were used to evaluate the performance of the URGs signature. Thereafter, a nomogram was constructed and evaluated.Results: A six-URGs signature was established to predict biochemical recurrence (BCR) of PCa, which included ARIH2, FBXO6, GNB4, HECW2, LZTR1 and RNF185. Kaplan-Meier curve and ROC curve analyses revealed good performance of the prognostic signature in both training cohort and validation cohort. Univariate and multivariate Cox analyses showed the signature was an independent prognostic factor for BCR of PCa in training cohort. Then a nomogram based on the URGs signature and clinicopathological factors was established and showed an accurate prediction for prognosis in PCa.Conclusion: Our study established a URGs prognostic signature and constructed a nomogram to predict the BCR of PCa. This study could help with individualized treatment and identify PCa patients with high BCR risks.

Impact of the introduction of novel hormonal agents on metastatic castration-resistant prostate cancer treatment choice

2019 ◽  
Vol 26 (2) ◽  
pp. 293-305 ◽  
Author(s):  
Halima Lahcene ◽  
Armen G Aprikian ◽  
Marie Vanhuyse ◽  
Jason Hu ◽  
Franck Bladou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Public Funding ◽  
Cancer Registries ◽  
Castration Resistant Prostate Cancer ◽  
University Hospitals ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Before And After ◽  
Mcgill University

Background Docetaxel-based chemotherapy has been the cornerstone of the management of symptomatic metastatic castration-resistant prostate cancer (mCRPC) since 2004. This study aimed to describe how real-world clinical practice was changed with the public funding of novel hormonal agents (abiraterone and enzalutamide) in Quebec. Methods We conducted a retrospective cohort study in two McGill University hospitals. Hospital-based cancer registries were used to select mCRPC patients in medical oncology departments from January 2010 to June 2014. Two groups according to mCRPC diagnosis year were built, with 2012 chosen as the cut-off year, corresponding to the year abiraterone was approved for public reimbursement in second-line in Quebec. Kaplan–Meier analysis was used to estimate time to first docetaxel prescription since mCRPC diagnosis before and after 2012. Cox regression was used to identify predictive factors of docetaxel and novel hormonal agent use. Results In our cohort, 308 patients diagnosed with mCRPC were selected with 162 patients in the pre-2012 group and 146 patients in the post-2012 group. The median age at mCRPC was 74.0 years old. At 12 months from diagnosis, 69% of patients received a prescription for docetaxel in the pre-2012 group comparatively to 53% in the post-2012 group. Factors that decreased the likelihood of docetaxel utilization were: age older than 80 at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3–0.7), mCRPC diagnosis after 2012 (HR: 0.6; 95%CI: 0.4–0.8), and asymptomatic disease at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3–0.7). Conclusion The introduction of novel hormonal agents reduced first-line and overall docetaxel utilization and delayed time to its initiation.

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation for prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 68-68 ◽  
Author(s):  
Phuoc T. Tran ◽  
Amol Narang ◽  
Ashwin Ram ◽  
Scott P. Robertson ◽  
Pei He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
High Risk ◽  
Low Risk ◽  
Risk Level ◽  
Treatment Intensification ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Risk Patients ◽  
Poor Outcomes

68 Background: In patients with localized prostate cancer undergoing radiation therapy (RT) +/- androgen deprivation therapy (ADT), an end of radiation (EOR) PSA obtained during the last week of RT may serve as an early post-treatment predictor of poor outcomes and identify patients in whom to pursue treatment intensification or novel therapies. Methods: We reviewed an IRB-monitored, prospectively acquired database of patients with prostate cancer treated with definitive RT at our institution from 1993-2007 (n=890). Patients with an available EOR PSA were divided into two cohorts and analyzed separately based on inclusion of ADT into the treatment regimen. EOR PSA thresholds of 0.5 ng/mL and 1.0 ng/mL were explored. Multivariate analysis was performed to determine prognostic factors for biochemical failure-free survival (BFFS, Phoenix criteria) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA thresholds. Results: Median age was 69 years, with an even distribution of NCCN low risk (33.5%), intermediate risk (34.0%), and high risk (32.5%) patients. Median RT dose was 7020 cGy, and 54.5% were treated with ADT. Median follow-up of the entire cohort was 11.7 yrs. EOR PSA level was available for the majority of patients (77.5%). On multivariate analysis, EOR PSA >0.5 ng/mL was significantly associated with worse BFFS (p<0.0001) and OS (p<0.0001). In the subset of patients undergoing RT with ADT for NCCN intermediate/high risk disease, 5 yr BFFS was more disparate based an EOR PSA threshold of 0.5 ng/mL (5 yr BFFS: 87.3% vs. 41.1%, p<0.001), than initial NCCN risk level (5 yr BFFS: 88.7% vs. 76.9%, p=0.038). In NCCN low risk patients undergoing definitive RT alone, an EOR PSA threshold of 1.0 ng/mL was significantly prognostic of outcome (5 yr BFFS: 100.0% vs. 88.6%, p=0.024). Conclusions: For NCCN intermediate/high risk patients undergoing RT with ADT, EOR PSA >0.5 ng/mL may represent a better surrogate for poor outcomes than initial risk group. In addition, NCCN low risk patients undergoing RT alone who obtained an EOR PSA ≤1.0 ng/mL experienced excellent BFFS. Prospective evaluation of the utility of EOR PSA should be explored.

Prognostic score to predict time to castration-resistance in underserved patients with metastatic prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16518-e16518
Author(s):  
Ankit Mangla ◽  
Muhammad Umair Mushtaq ◽  
Udit Yadav ◽  
Ahmed T Ahmed ◽  
Jiaxiang Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Cox Regression ◽  
Prognostic Score ◽  
Tertiary Care ◽  
Specific Antigen ◽  
Care Hospital ◽  
Castration Resistance ◽  
Neutrophil Lymphocyte Ratio ◽  
Kaplan Meier

e16518 Background: This study aimed to identify predictors of time to castration-resistance prostate cancer (tCRPC) from initial diagnosis of metastatic prostate cancer (mPC) and develop a prognostic score in the underserved population of an inner-city tertiary care hospital. Methods: We retrospectively reviewed charts of 278 men diagnosed with mPC between 2001 and 2015, of which 155 patients were analyzed. Socio-demographic, clinical and pathologic factors were ascertained at the time of diagnosis. Kaplan-Meier and cox regression analyses were done to explore correlates tCRPC. Crude (HR) and adjusted (aHR) hazard ratios with 95% confidence intervals (CI) were obtained. Results: Over a median follow-up of 46 months (95% CI 23-69), 73.5% of men developed castration-resistance. Median tCRPC was 16 months (95% CI 12.5-19.5). All patients received medical or surgical castration at the time of diagnosis. Significant correlates of short tCRPC included: prostate specific antigen >20 ng/mL (HR 2.56, 95% CI 1.25-5.23, P=0.010), core involvement >50% (HR 2.11, 95% CI 1.43-3.11, P<0.001), bone metastases (HR 2.94, 95% CI 1.36-6.35, P=0.006), visceral metastases (HR 01.65, 95% CI 1.08-2.53, P=0.021), hemoglobin <10 g/dL (HR 2.02, 95% CI 1.26-3.23, P=0.003), alkaline phosphatase (ALP) >240 U/L (HR 2.42, 95% CI 1.62-3.61, P<0.001), lactate dehydrogenase (LDH) >200 U/L (HR 1.68, 95% CI 1.16-2.43, P=0.006) and neutrophil-lymphocyte ratio >2.4 (HR 1.50, 95% CI 1.03-2.20, P=0.035). In multivariate model, core involvement >50% (aHR 2.99, 95% CI 1.79-5.01, P<0.001), ALP >240 U/L (aHR 2.08, 95% CI 1.13-3.84, P=0.019) and LDH >200 U/L (aHR 1.71, 95% CI 1.02-2.86, P=0.043) independently predicted short tCRPC and each factor decreased tCRPC by almost 50%. Mean prognostic score (PS), based on 1 point for each independent predictor (scale 0-3), was 1.23 (SD 0.91) and significantly predicted short tCRPC (P<0.001). [Table] Conclusions: Our PS based on core involvement (>50%), high ALP (>240 U/L) and high LDH (>200 U/L) significantly predicts tCRPC in men with mPC. Prospective studies are warranted to further validate this score. [Table: see text]

Germline variant in SLCO2B1 and response to abiraterone acetate plus prednisone (AA) in men with metastatic castration-resistant prostate cancer (mCRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 311-311
Author(s):  
Andrew W Hahn ◽  
Darshan Patel ◽  
David Michael Gill ◽  
Camryn Froerer ◽  
Roberto Nussensveig ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Salt Lake ◽  
Organic Anion ◽  
Predictive Biomarkers ◽  
Organic Anion Transporter ◽  
Nucleotide Polymorphisms ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Anion Transporter

311 Background: Currently, there are no predictive biomarkers of response to AA in mCRPC routinely used in the clinic. SLCO2B1 encodes a sodium-independent organic anion transporter that mediates transport of endogenous sex hormones and drugs, including AA, into tissue. Single nucleotide polymorphisms (SNPs) in SLCO2B1 are a validated predictive biomarker of response to androgen deprivation therapy in hormone sensitive prostate cancer. In a recent pre-clinical study, the AA/AG genotype for rs12422149 and the AA genotype for rs1789693 of SLCO2B1 had significantly higher mean tissue abiraterone levels. We hypothesize that the variant allele for rs12422149 and rs1789693 are predictive of improved response to AA in mCRPC. Methods: Clinical data and samples were analyzed from a prospective prostate cancer registry at the University of Utah (Salt Lake City, UT). Genotyping was performed using the Illumina OmniExpress genotyping platform. Primary endpoint was progression-free survival (PFS) on first-line AA in men with mCRPC. We performed pre-specified multivariate Cox regression analyses to assess the independent predictive value of SLCO2B1 rs12422149 and rs1789693 on PFS on AA (table). Results: 76 men with mCRPC treated with first-line AA were included. In a multivariate analysis for rs12422149, a trend towards improved median PFS was seen with the AG genotype (11.2 months) vs. the GG genotype (6.4 months) (HR 0.50, 95% CI 0.24-1.02, p=0.056). No such correlation was seen with rs1789693 genotypes. Conclusions: Consistent with pre-clinical studies, the AG genotype in rs12422149 of SLCO2B1 may be predictive of response to AA in men with mCRPC. This hypothesis-generating data needs further interrogation in larger and independent cohorts. [Table: see text]

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