scholarly journals Aberrant DOCK2, GRASP, HIF3A and PKFP Hypermethylation has Potential as a Prognostic Biomarker for Prostate Cancer

2019 ◽  
Vol 20 (5) ◽  
pp. 1173 ◽  
Author(s):  
Marianne Bjerre ◽  
Siri Strand ◽  
Maibritt Nørgaard ◽  
Helle Kristensen ◽  
Anne Rasmussen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Blood Cells ◽  
Cox Regression ◽  
High Sensitivity ◽  
Cancer Tissue ◽  
Dna Hypermethylation ◽  
450K Array ◽  
Systematic Analysis ◽  
Tissue Samples ◽  
Independent Population

Prostate cancer (PCa) is a clinically heterogeneous disease and currently, accurate diagnostic and prognostic molecular biomarkers are lacking. This study aimed to identify novel DNA hypermethylation markers for PCa with future potential for blood-based testing. Accordingly, to search for genes specifically hypermethylated in PCa tissue samples and not in blood cells or other cancer tissue types, we performed a systematic analysis of genome-wide DNA methylation data (Infinium 450K array) available in the Marmal-aid database for 4072 malignant/normal tissue samples of various types. We identified eight top candidate markers (cg12799885, DOCK2, FBXO30, GRASP, HIF3A, MOB3B, PFKP, and TPM4) that were specifically hypermethylated in PCa tissue samples and hypomethylated in other benign and malignant tissue types, including in peripheral blood cells. Potential as diagnostic and prognostic biomarkers was further assessed by the quantitative methylation specific PCR (qMSP) analysis of 37 nonmalignant and 197 PCa tissue samples from an independent population. Here, all eight hypermethylated candidates showed high sensitivity (75–94%) and specificity (84–100%) for PCa. Furthermore, DOCK2, GRASP, HIF3A and PKFP hypermethylation was significantly associated with biochemical recurrence (BCR) after radical prostatectomy (RP; 197 patients), independent of the routine clinicopathological variables. DOCK2 is the most promising single candidate marker (hazard ratio (HR) (95% confidence interval (CI)): 1.96 (1.24–3.10), adjusted p = 0.016; multivariate cox regression). Further validation studies are warranted and should investigate the potential value of these hypermethylation candidate markers for blood-based testing also.

DNA Methylation Signatures for Prediction of Biochemical Recurrence After Radical Prostatectomy of Clinically Localized Prostate Cancer

2013 ◽  
Vol 31 (26) ◽  
pp. 3250-3258 ◽  
Author(s):  
Christa Haldrup ◽  
Kamilla Mundbjerg ◽  
Else Marie Vestergaard ◽  
Philippe Lamy ◽  
Peter Wild ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Specific Area ◽  
Dna Hypermethylation ◽  
Tissue Samples ◽  
Delayed Treatment

PurposeDiagnostic and prognostic tools for prostate cancer (PC) are suboptimal, causing overtreatment of indolent PC and risk of delayed treatment of aggressive PC. Here, we identify six novel candidate DNA methylation markers for PC with promising diagnostic and prognostic potential.MethodsMicroarray-based screening and bisulfite sequencing of 20 nonmalignant and 29 PC tissue specimens were used to identify new candidate DNA hypermethylation markers for PC. Diagnostic and prognostic potential was evaluated in 35 nonmalignant prostate tissue samples, 293 radical prostatectomy (RP) samples (cohort 1, training), and 114 malignant RP samples (cohort 2, validation) collected in Denmark, Switzerland, Germany, and Finland. Sensitivity and specificity for PC were evaluated by receiver operating characteristic analyses. Correlations between DNA methylation levels and biochemical recurrence were assessed using log-rank tests and univariate and multivariate Cox regression analyses.ResultsHypermethylation of AOX1, C1orf114, GAS6, HAPLN3, KLF8, and MOB3B was highly cancer specific (area under the curve, 0.89 to 0.98). Furthermore, high C1orf114 methylation was significantly (P < .05) associated with biochemical recurrence in multivariate analysis in cohort 1 (hazard ratio [HR], 3.10; 95% CI, 1.89 to 5.09) and was successfully validated in cohort 2 (HR, 3.27; 95% CI, 1.17 to 9.12). Moreover, a significant (P < .05) three-gene prognostic methylation signature (AOX1/C1orf114/HAPLN3), classifying patients into low- and high-methylation subgroups, was trained in cohort 1 (HR, 1.91; 95% CI, 1.26 to 2.90) and validated in cohort 2 (HR, 2.33; 95% CI, 1.31 to 4.13).ConclusionWe identified six novel candidate DNA methylation markers for PC. C1orf114 hypermethylation and a three-gene methylation signature were independent predictors of time to biochemical recurrence after RP in two PC patient cohorts.

scholarly journals EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1410
Author(s):  
Anna Buchholz ◽  
Aurelia Vattai ◽  
Sophie Fürst ◽  
Theresa Vilsmaier ◽  
Christina Kuhn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Vulvar Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Common Finding ◽  
Cancer Tissue ◽  
Vulvar Carcinoma ◽  
Tissue Samples

New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.

scholarly journals Downregulation and Prognostic Performance of MicroRNA 224 Expression in Prostate Cancer

2013 ◽  
Vol 59 (1) ◽  
pp. 261-269 ◽  
Author(s):  
Konstantinos Mavridis ◽  
Konstantinos Stravodimos ◽  
Andreas Scorilas
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Prognostic Indicator ◽  
Disease Stage ◽  
Clinical Value ◽  
Prostate Tumors ◽  
Tissue Samples ◽  
Total Rna

INTRODUCTION The extensive use of prostate-specific antigen as a general prostate cancer biomarker has introduced the hazards of overdiagnosis and overtreatment. Recent studies have revealed the immense biomarker capacity of microRNAs (miRNAs) in prostate cancer. The aim of this study was to analyze the expression pattern of miR-224, a cancer-related miRNA, in prostate tumors and investigate its clinical utility. METHODS Total RNA was isolated from 139 prostate tissue samples. After the polyadenylation of total RNA by poly(A) polymerase, cDNA was synthesized with a suitable poly(T) adapter. miR-224 expression was assessed by quantitative real-time PCR and analyzed with the comparative quantification cycle method, Cq(2−ΔΔCq). We performed comprehensive biostatistical analyses to explore the clinical value of miR-224 in prostate cancer. RESULTS miR-224 expression was significantly downregulated in malignant samples compared with benign samples (P &lt; 0.001). Higher miR-224 expression levels were found in prostate tumors that were less aggressive (P = 0.017) and in an earlier disease stage (P = 0.018). Patients with prostate cancer who were positive for miR-224 had significantly enhanced progression-free survival intervals compared with miR-224–negative patients (P = 0.021). Univariate bootstrap Cox regression confirmed that miR-224 was associated with favorable prognosis (hazard ratio 0.314, P = 0.013); nonetheless, multivariate analysis, adjusted for conventional markers, did not identify miR-224 as an independent prognostic indicator. CONCLUSIONS miR-224 is aberrantly expressed in prostate cancer. Its assessment by cost-effective quantitative molecular methodologies could provide a useful biomarker for prostate cancer.

scholarly journals Epigenetic Markers for Molecular Detection of Prostate Cancer

2007 ◽  
Vol 23 (1-2) ◽  
pp. 31-41 ◽  
Author(s):  
Vera L. Costa ◽  
Rui Henrique ◽  
Carmen Jerónimo
Keyword(s):  
Prostate Cancer ◽  
Sensitivity And Specificity ◽  
Prostate Cancer Risk ◽  
High Sensitivity ◽  
Promoter Hypermethylation ◽  
Clinical Samples ◽  
Screening Methods ◽  
Tissue Samples ◽  
Age Related ◽  
Small Set

Prostate cancer is a highly prevalent malignancy, which is clinically silent but curable while organ-confined. Because available screening methods show poor sensitivity and specificity, the development of new molecular markers is warranted. Epigenetic alterations, mainly promoter hypermethylation of cancer-related genes, are common events in prostate cancer and might be used as cancer biomarkers. Moreover, the development of quantitative, high-throughput techniques to assess promoter methylation enabled the simultaneous screening of multiple clinical samples. From the numerous cancer-related genes hypermethylated in prostate cancer only a few proved to be strong candidates to become routine biomarkers. This small set of genes includesGSTP1,APC,RARβ2,Cyclin D2,MDR1, andPTGS2. Single and/or multigene analyses demonstrated the feasibility of detecting early prostate cancer, with high sensitivity and specificity, in body fluids (serum, plasma, urine, and ejaculates) and tissue samples. In addition, quantitative hypermethylation of several genes has been associated with clinicopathologic features of tumor aggressiveness, and also reported as independent prognostic factor for relapse. The identification of age-related methylation at specific loci and the differential frequency of methylation among ethnical groups, also provided interesting data linking methylation and prostate cancer risk. Although large trials are needed to validate these findings, the clinical use of these markers might be envisaged for the near future.

scholarly journals Evaluation of GNMT Gene Expression in Prostate Cancer Tissues using Real-Time PCR

2021 ◽  
Author(s):  
Niloofar Dehghani ◽  
Masoud Salehipour ◽  
Babak Javanmard
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Real Time ◽  
Real Time Pcr ◽  
Prostatic Hyperplasia ◽  
Expression Level ◽  
P Value ◽  
Cancer Tissue ◽  
Tissue Samples

Introduction: Prostate cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide. In the present study, the expression level of glycine N-methyl transferase gene (GNMT) was investigated in prostate cancer tissue. The GNMT enzyme is encoded by the GNMT gene. Increased GNMT gene expression increases the conversion of glycine to sarcosine and results in the elevated levels of sarcosine in blood and urine. Methods: The expression level of GNMT gene in tissue samples of patients with prostate cancer was compared with those with benign prostatic hyperplasia using Real-Time PCR technique. Results: The GNMT gene expression level increased significantly in prostate cancer patients compared with those with benign prostatic hyperplasia (p-value <0.001). In addition, the expression level of GNMT gene was stage-dependent and  significant increases were observed in all stages of prostate cancer compared with those with benign prostatic hyperplasia (p-value <0.001). Conclusion: The concentration of sarcosine is controlled by GNMT and it seems that increasing the expression level of GNMT gene increases the level of sarcosine concentration. Thus, it appears that increased levels of GNMT expression occur in the early stages of prostate cancer. Therefore, periodic measurement of GNMT expression levels can detect prostate cancer before it forms a cancer cell and invades other tissues.

PITX2 methylation and biochemical recurrence in postradical prostatectomy prostate cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5124-5124
Author(s):  
E. Heiden ◽  
G. Weiss ◽  
L. Banez ◽  
S. Freedland ◽  
L. Sun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Methylation Status ◽  
Gene Promoter ◽  
Surgical Margins ◽  
Rank Test ◽  
Clinical Tool ◽  
Prognostic Information ◽  
Tissue Samples

5124 Background: PITX2 is a bicoid-related transcription factor induced by the Wnt pathway and required for effective cell-type-specific proliferation during development. We previously reported prognostic potential of PITX2 gene promoter methylation for outcome prediction in breast and prostate cancer (PC) patients. Radical prostatectomy (RP) is potentially curative in patients with clinically localized PC. However, biochemical recurrence (BCR) affects 15–30% of patients undergoing RP. In the current study, we validate PITX2 methylation status as a predictor of BCR following RP. Methods: PITX2 methylation status was assessed in formalin-fixed paraffin-embedded RP tumor tissue samples from 476 patients from four different institutions in USA and Europe using customized microarrays. Associations between PITX2 methylation and BCR were assessed using log-rank test and Cox regression controlling for PC features. Results: In multivariate analysis, patients with a high methylation status were at significantly higher risk for BCR compared to patients with low methylation status (HR = 3.0; 95%CI = 2.0–4.5; p < 10-5). BCR-free survival at five years after surgery was 85% and 61% for patients in the low and high methylation group, respectively. In patients with pathological Gleason 7 tumors, the relative risk of suffering BCR was twice as high for a patient with high PITX2 methylation relative to patients with low PITX2 methylation (HR = 2.0; 95%CI = 1.2–3.3; p = 0.005). Moreover, PITX2 methylation status was significant in the group of patients with tumor involvement of the surgical margins in the prostatectomy specimen. (HR = 3.36, 95% CI: 2.24–5.06, p = 0.001). Conclusions: PITX2 methylation status identifies PC patients most likely to experience BCR. This test independently adds to prognostic information provided by standard clinico-pathological analyses improving stratification of RP patients into high- or low-risk for BCR. This new clinical tool would be of particular benefit in assessment of intermediate-risk patients (Gleason 7) or patients with positive surgical margins wherein risk stratification remains a challenge. [Table: see text]

Value of NADiA ProsVue on the CAPRA-S nomogram for predicting postprostatectomy clinical recurrence.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 139-139 ◽  
Author(s):  
Judd W. Moul ◽  
Hans Lilja ◽  
Raymond Lance ◽  
Robert Vessella ◽  
Jonathan E. McDermed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Risk Groups ◽  
Study Cohort ◽  
Clinical Recurrence ◽  
Prognostic Test ◽  
Independent Population ◽  
Imaging Results ◽  
Reduced Risk

139 Background: The post-radical prostatectomy (RP) CAPRA-S nomogram stratifies men into low, intermediate and high risk groups for biochemical recurrence (BCR) and proved accurate for predicting 3 and 5 year BCR rates in a large study cohort. NADiA ProsVue is a prognostic test that identifies men at reduced risk of clinically recurrent prostate cancer when used with traditional risk factors. We assessed ProsVue, a prognostic test for identifying post-RP clinical recurrence, in an independent population of men classified into low, intermediate and high CAPRA-S risk groups. Methods: The 304 men in the ProsVue 510(k) study were categorized into low (scores 0-2), intermediate (3-5) and high (≥6) CAPRA-S risk groups. Men were categorized as “at reduced risk” or “not at reduced risk” using a 2.0 pg/mL/month ProsVue cutpoint. Clinical recurrence was defined by positive biopsy or imaging results or death due to prostate cancer. Clinical progression-free survival (cPFS) was determined between subgroups using univariate Cox regression and Kaplan-Meier survival analyses and Wilcoxon and log-rank p values were reported. Results: Recurrence occurred in 8/156 (5.1%), 20/93 (21.5%) and 32/55 (58.2%) of men in the low, intermediate, and high CAPRA-S risk groups, respectively (P<0.0001). After 3, 5, 8 and 15 year followup, men in all CAPRA-S risk groups with ProsVue results ≤2.0 had significantly longer cPFS compared to men with results >2.0. The differences are marked as early as 3 years post-RP in the intermediate and high risk groups. Conclusions: ProsVue added significant prognostic value for identifying risk of clinical recurrence within low, intermediate and high CAPRA-S risk groups. ProsVue is the strongest independent predictor of clinical recurrence of prostate cancer post-RP. [Table: see text]

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.

scholarly journals Development and validation of a set of novel and robust 4-lncRNA-based nomogram predicting prostate cancer survival by bioinformatics analysis

2020 ◽  
Author(s):  
Peng Zhang ◽  
Aiyu Wang ◽  
Liming Dong ◽  
Xuefeng Zhang
Keyword(s):  
Prostate Cancer ◽  
Extracellular Matrix ◽  
Regression Analysis ◽  
Cell Membrane ◽  
Sensitivity And Specificity ◽  
Cox Regression ◽  
Functional Enrichment ◽  
Prediction Ability ◽  
Tissue Samples ◽  
Cox Regression Analysis

Abstract Background and Objective: There is significant heterogeneity between cellular composition and patient outcome in prostate cancer (PCa). Accumulating evidence shows that long noncoding RNAs (lncRNAs) possess great potential in the diagnosis and prognosis of PCa with biological and clinical significance. Therefore, this study aimed to construct an lncRNA-based signature to more accurately predict the prognosis of different PCa patients, so as to improve patient management and prognosis. Methods The Cancer Genome Atlas (TCGA) database was used to download RNA-seq expression data together with the clinical information of 499 PCa tissue samples as well as 52 corresponding non-carcinoma tissue samples. Differently expressed lncRNAs (DElncRNAs) were selected based on tumor tissues and non-carcinoma samples. Through univariate and multivariate Cox regression analysis, this study constructed a 4 lncRNAs-based prognosis nomogram for the classification and prediction of survival risk in patients with PCa. The receiver operating characteristic (ROC) curve was plotted for detecting and validating our prediction model sensitivity and specificity. In addition, univariate as well as multivariate Cox regression was conducted to examine whether the constructed lncRNA signature’s prediction ability was independent of additional clinicopathological variables (like age, Gleason score, N stage, T stage and M stage) among PCa cases. Possible biological functions for those prognostic lncRNAs were predicted through gene ontology (GO) together with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on those 4 protein-coding genes (PCGs) related to lncRNAs. Results A total of 451 differently expressed lncRNAs (DElncRNAs) related to the overall survival (OS) rate for PCa cases were screened from 3838 lncRNAs in the TCGA database. Four lncRNAs (HOXB-AS3, YEATS2-AS1, LINC01679, PRRT3-AS1) were extracted after univariate as well as multivariate COX regression analysis for classifying patients into high and low-risk groups by different OS rates. As suggested by ROC analysis, our proposed model showed high sensitivity and specificity. Independent prognostic capability of the model from other clinicopathological factors was indicated through further analysis. Based on functional enrichment, those action sites for prognostic lncRNAs were mostly located in the extracellular matrix and cell membrane, and their functions are mainly associated with the adhesion, activation and transport of the components across the extracellular matrix or cell membrane. Conclusion Our current study successfully identifies a novel four-lncRNA candidate, which can provide more convincing evidence for prognosis in addition to the traditional clinicopathological indicators to predict the PCa survival, and laying the foundation for offering potentially novel therapeutic treatment. Additionally, this study sheds more lights on the PCa-related molecular mechanisms.

scholarly journals Cholesterol Synthesis Pathway Genes in Prostate Cancer are consistently downregulated when tissue confounding is minimized

2017 ◽  
Author(s):  
Morten Beck Rye ◽  
Helena Bertilsson ◽  
Maria K. Andersen ◽  
Kjersti Rise ◽  
Tone F. Bathen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Expression Analysis ◽  
Cholesterol Synthesis ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Cellular Cholesterol ◽  
Cholesterol Levels ◽  
Heterogeneous Tissue

AbstractThe relationship between cholesterol and prostate cancer has been extensively studied for decades, where high levels of cellular cholesterol are generally associated with cancer progression and less favorable outcomes. However, the role of in vivo cellular cholesterol synthesis in this process is unclear, and data on the transcriptional activity of cholesterol synthesis pathway genes in tissue from prostate cancer patients are inconsistent. A common problem with cancer tissue data from patient cohorts is the presence of heterogeneous tissue which confounds molecular analysis of the samples. In this study we present a method to minimize systematic confounding from stroma tissue in seven patient cohorts consisting of 1713 prostate cancer and 230 normal tissue samples. When confounding was minimized, differential gene expression analysis over all cohorts showed robust and consistent downregulation of nearly all genes in the cholesterol synthesis pathway. Additional analysis also identified cholesterol synthesis as the most significantly altered metabolic pathway in prostate cancer. This surprising observation is important for our understanding of how prostate cancer cells regulate cholesterol levels in vivo. Moreover, we show that tissue heterogeneity explains the lack of consistency in previous expression analysis of cholesterol synthesis genes in prostate cancer.

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