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Project description:Prostate cancer (PCa) is a major health burden world-wide and despite early treatment, a very large proportion of patients present with biochemical recurrence (BCR) post-treatment, reflected by a rise in PSA over a clinical threshold. Novel transcriptomic and epigenomic biomarkers can provide a powerful tool for clinical management of PCa. Here we provide matched high-depth RNA-Sequencing and array-based genome-wide DNA methylome data of PCa patients (n = 17) with, or without, evidence of BCR following early radical prostatectomy. We have utilized Formalin-Fixed Paraffin-Embedded tissues to generate this data and included technical replicates to provide further validity of the data. We describe the sample features, experimental design, methods and bioinformatic pipeline for processing these multi-omic data. Importantly, we provide comprehensive clinical, histopathological, and follow-up data for each patient to enable correlating transcriptome and methylome features with clinical features. Our data will contribute towards the efforts of developing epigenomic and transcriptomic markers for BCR and also facilitate a deeper understanding of the molecular basis of PCa recurrence.
2025-03-23 | GSE277820 | GEO
Project description:Prostate cancer (PCa) is a major health burden world-wide and despite early treatment, a very large proportion of patients present with biochemical recurrence (BCR) post-treatment, reflected by a rise in PSA over a clinical threshold. Novel transcriptomic and epigenomic biomarkers can provide a powerful tool for clinical management of PCa. Here we provide matched RNA-Sequencing and array-based genome-wide DNA methylome data of PCa patients (n = 17) with, or without, evidence of BCR following early radical prostatectomy. We have utilized Formalin-Fixed Paraffin-Embedded tissues to generate this data and included technical replicates to provide further validity of the data. We describe the sample features, experimental design, methods and bioinformatic pipeline for processing these multi-omic data. Importantly, we provide comprehensive clinical, histopathological, and follow-up data for each patient to enable correlating transcriptome and methylome features with clinical features. Our data will contribute towards the efforts of developing epigenomic and transcriptomic markers for BCR and also facilitate a deeper understanding of the molecular basis of PCa recurrence.
2025-03-23 | GSE278135 | GEO
Project description:Genome-scale DNA methylome and transcriptome profiles of early prostate cancer recurrence after prostatectomy
| PRJNA1189156 | ENA
Project description:Genome-scale DNA methylome and transcriptome profiles of early prostate cancer recurrence after prostatectomy [methylation array]
| PRJNA1164270 | ENA
Project description:Genome-scale DNA methylome and transcriptome profiles of early prostate cancer recurrence after prostatectomy [RNA-seq]
| PRJNA1165752 | ENA
Project description:BackgroundProstate cancer (PCa) is a leading reason of death in men and the most diagnosed malignancies in the western countries at the present time. After radical prostatectomy (RP), nearly 30% of men develop clinical recurrence with high serum prostate-specific antigen levels. An important challenge in PCa research is to identify effective predictors of tumor recurrence. The molecular alterations in microRNAs are associated with PCa initiation and progression. Several miRNA microarray studies have been conducted in recurrence PCa, but the results vary among different studies.MethodsWe conducted a meta-analysis of 6 available miRNA expression datasets to identify a panel of co-deregulated miRNA genes and overlapping biological processes. The meta-analysis was performed using the 'MetaDE' package, based on combined P-value approaches (adaptive weight and Fisher's methods), in R version 3.3.1.ResultsMeta-analysis of six miRNA datasets revealed miR-125A, miR-199A-3P, miR-28-5P, miR-301B, miR-324-5P, miR-361-5P, miR-363*, miR-449A, miR-484, miR-498, miR-579, miR-637, miR-720, miR-874 and miR-98 are commonly upregulated miRNA genes, while miR-1, miR-133A, miR-133B, miR-137, miR-221, miR-340, miR-370, miR-449B, miR-489, miR-492, miR-496, miR-541, miR-572, miR-583, miR-606, miR-624, miR-636, miR-639, miR-661, miR-760, miR-890, and miR-939 are commonly downregulated miRNA genes in recurrent PCa samples in comparison to non-recurrent PCa samples. The network-based analysis showed that some of these miRNAs have an established prognostic significance in other cancers and can be actively involved in tumor growth. Gene ontology enrichment revealed many target genes of co-deregulated miRNAs are involved in "regulation of epithelial cell proliferation" and "tissue morphogenesis". Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these miRNAs regulate cancer pathways. The PPI hub proteins analysis identified CTNNB1 as the most highly ranked hub protein. Besides, common pathway analysis showed that TCF3, MAX, MYC, CYP26A1, and SREBF1 significantly interact with those DE miRNA genes. The identified genes have been known as tumor suppressors and biomarkers which are closely related to several cancer types, such as colorectal cancer, breast cancer, PCa, gastric, and hepatocellular carcinomas. Additionally, it was shown that the combination of DE miRNAs can assist in the more specific detection of the PCa and prediction of biochemical recurrence (BCR).ConclusionWe found that the identified miRNAs through meta-analysis are candidate predictive markers for recurrent PCa after radical prostatectomy.
| S-EPMC5484492 | biostudies-literature
Project description:BackgroundCurrent clinical tools have limited accuracy in differentiating patients with localized prostate cancer who are at risk of recurrence from patients with indolent disease. We aimed to identify a gene expression signature that jointly with clinical variables could improve upon the prediction of clinical recurrence after RP for patients with stage T2 PCa.MethodsThe study population includes consented patients who underwent a radical retropubic prostatectomy (RP) and bilateral pelvic lymph node dissection at the University of Southern California in the PSA-era (1988-2008). We used a nested case-control study of 187 organ-confined patients (pT2N0M0): 154 with no recurrence ("controls") and 33 with clinical recurrence ("cases"). RNA was obtained from laser capture microdissected malignant glands representative of the overall Gleason score of each patient. Whole genome gene expression profiles (29,000 transcripts) were obtained using the Whole Genome DASL HT platform (Illumina, Inc). A gene expression signature of PCa clinical recurrence was identified using stability selection with elastic net regularized logistic regression. Three existing datasets generated with the Affymetrix Human Exon 1.0ST array were used for validation: Mayo Clinic (MC, n = 545), Memorial Sloan Kettering Cancer Center (SKCC, n = 150), and Erasmus Medical Center (EMC, n = 48). The areas under the ROC curve (AUCs) were obtained using repeated fivefold cross-validation.ResultsA 28-gene expression signature was identified that jointly with key clinical variables (age, Gleason score, pre-operative PSA level, and operation year) was predictive of clinical recurrence (AUC of clinical variables only was 0.67, AUC of clinical variables, and 28-gene signature was 0.99). The AUC of this gene signature fitted in each of the external datasets jointly with clinical variables was 0.75 (0.72-0.77) (MC), 0.90 (0.86-0.94) (MSKCC), and 0.82 (0.74-0.91) (EMC), whereas the AUC for clinical variables only in each dataset was 0.72 (0.70-0.74), 0.86 (0.82-0.91), and 0.76 (0.67-0.85), respectively.ConclusionsWe report a novel gene-expression based classifier identified using agnostic approaches from whole genome expression profiles that can improve upon the accuracy of clinical indicators to stratify early stage localized patients at risk of clinical recurrence after RP. Prostate 76:1239-1256, 2016. © 2016 Wiley Periodicals, Inc.
| S-EPMC9015679 | biostudies-literature
Project description:Patients with prostate cancer (PCa) have a variable prognosis. It is challenging to recognize the progressive disease. In this study, we focused on TSPAN1, a new member of the tetraspanin family. Its expression was decreased in progressive PCa and was an independent prognosis factor of biochemical recurrence after radical prostatectomy. In vitro, knockdown and overexpression of TSPAN1 in PCa cell lines showed that TSPAN1 could inhibit cell proliferation and migration. TSPAN1 was positive related to PTEN in both clinical specimen and mouse models. The combination of these two markers could increase their prognosis value especially in low risk patients. In vitro TSPAN1 knockdown resulted in increased Akt phosphorylation and caused evident cell cycle transition from G1 to S phase. Our data suggests that TSPAN1 is a valuable marker to recognize more progressive PCa.
| S-EPMC5325364 | biostudies-literature
Project description:HOXB13 is a prostate cancer susceptibility gene which shows a cancer predisposing (G84E) mutation in 0.1-0.6% of males. We analyzed the prognostic impact of HOXB13 expression by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancers. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor (AR) and prostate specific antigen (PSA) as well as molecular subtypes defined by ERG status and genomic deletions of 3p, 5q, 6q, and PTEN. HOXB13 immunostaining was detectable in 51.7% of 10,216 interpretable cancers and considered strong in 9.6%, moderate in 19.7% and weak in 22.3% of cases. HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each). The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA. Co-expression analysis identified a subset of tumors with high HOXB13 and AR but low PSA expression that had a particularly poor prognosis. HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.
| S-EPMC4494977 | biostudies-literature
Project description:The metabolic syndrome (MetS) comprises a constellation of risk factors associated with an increased risk for cardiovascular disease. Components of MetS have emerged as putative risk factors for prostate carcinoma. In this study, we examine the association between three features of the MetS (obesity, hypertension and diabetes) and the risk of biochemical recurrence (BCR) after radical prostatectomy (RP).We examined data from 1428 men in the University of Michigan Prostate Cancer Data Bank who elected to have RP as their primary treatment. We calculated body mass index from patients' weight and height measured at the time of prostate cancer diagnosis. We used the University of Michigan's Electronic Medical Record Search Engine to identify subjects with hypertension and/or diabetes before their prostate cancer diagnosis.Of 1428 men who underwent RP, 107 (8%) subsequently developed BCR with a median length of follow-up post-surgery of 3.6 years. Obesity and hypertension were each associated with an increased risk of BCR (adjusted hazard ratio (aHR) = 1.37; 95% CI 0.92-2.09 and aHR = 1.51, 95% CI 1.01-2.26), whereas no association was observed between diabetes and BCR (aHR = 0.73; 95% CI 0.40-1.33).Obesity and hypertension were each associated with an increased risk for BCR of prostate cancer after RP, independent of age at diagnosis and tumor pathological features. Given the increasing rates of obesity, hypertension and prostate cancer, a better understanding of the relationship between these entities is of significant public health importance. Elucidation of the involved pathogenic mechanisms will be needed to establish causality.
| S-EPMC3860174 | biostudies-literature