Dataset Information

Integrative metabolic and transcriptomic profiling of prostate cancer tissue containing reactive stroma.

ABSTRACT: Reactive stroma is a tissue feature commonly observed in the tumor microenvironment of prostate cancer and has previously been associated with more aggressive tumors. The aim of this study was to detect differentially expressed genes and metabolites according to reactive stroma content measured on the exact same prostate cancer tissue sample. Reactive stroma was evaluated using histopathology from 108 fresh frozen prostate cancer samples gathered from 43 patients after prostatectomy (Biobank1). A subset of the samples was analyzed both for metabolic (n?=?85) and transcriptomic alterations (n?=?78) using high resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) and RNA microarray, respectively. Recurrence-free survival was assessed in patients with clinical follow-up of minimum five years (n?=?38) using biochemical recurrence (BCR) as endpoint. Multivariate metabolomics and gene expression analysis compared low (?15%) against high reactive stroma content (?16%). High reactive stroma content was associated with BCR in prostate cancer patients even when accounting for the influence of Grade Group (Cox hazard proportional analysis, p?=?0.013). In samples with high reactive stroma content, metabolites and genes linked to immune functions and extracellular matrix (ECM) remodeling were significantly upregulated. Future validation of these findings is important to reveal novel biomarkers and drug targets connected to immune mechanisms and ECM in prostate cancer. The fact that high reactive stroma grading is connected to BCR adds further support for the clinical integration of this histopathological evaluation.

SUBMITTER: Andersen MK

PROVIDER: S-EPMC6155140 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrative metabolic and transcriptomic profiling of prostate cancer tissue containing reactive stroma.

Andersen Maria K MK Rise Kjersti K Giskeødegård Guro F GF Richardsen Elin E Bertilsson Helena H Størkersen Øystein Ø Bathen Tone F TF Rye Morten M Tessem May-Britt MB

Scientific reports 20180924 1

Reactive stroma is a tissue feature commonly observed in the tumor microenvironment of prostate cancer and has previously been associated with more aggressive tumors. The aim of this study was to detect differentially expressed genes and metabolites according to reactive stroma content measured on the exact same prostate cancer tissue sample. Reactive stroma was evaluated using histopathology from 108 fresh frozen prostate cancer samples gathered from 43 patients after prostatectomy (Biobank1). ...[more]

PMID: 30250137

Similar Datasets

Project description:BackgroundComprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging.Patients and methodsWe developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing.ResultsWe identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for all 8 tumor/lymph node metastasis pairs, consistent with limited heterogeneity amongst driving events. MiPC and exome sequencing were performed on separately isolated conventional acinar PCa and prostatic small cell carcinoma (SCC) components from the same FFPE resection specimen to enable direct comparison of histologically distinct components. While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations.ConclusionsOur results demonstrate the feasibility of integrative profiling of routine PCa specimens, which may have utility for understanding disease biology and enabling personalized medicine applications.

Dataset Information

Integrative metabolic and transcriptomic profiling of prostate cancer tissue containing reactive stroma.

Publications

Integrative metabolic and transcriptomic profiling of prostate cancer tissue containing reactive stroma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets