Dataset Information

Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores.

ABSTRACT: The recent developments in anti-angiogenic and immunomodulatory drugs show that the tumour micro-environment (TME) becomes increasingly important in cancer research. Here we investigated the correlation between the Gleason score (GS) and the TME by comparing tissue expression profiles of steroid hormone receptors, cancer activated fibroblast (CAF) markers and vessel densities between different GS groups. Therefore, matched patient cohorts were composed for different GS (6-7-8). Tissue micro-arrays with 6 samples/patient were processed for immunohistochemistry. Stained slides were digitised, stroma and epithelium were selectively annotated, and all selected areas were quantitatively analysed for marker expression. The most striking findings were decreased stromal expression levels of several steroid hormone receptors, increased CAF-phenotypes and increased vessel densities in high GS prostate cancer compared to low GS prostate cancer and paired prostate non-tumour tissue. The present data reveal a complex correlation between prostate cancer differentiation and TME components and suggest that different GS can be associated with different possible actionable targets in the TME. The use of standardised digital image analysis tools generated robust and reproducible quantitative data, which is novel and more informative compared to the classic semi-quantitative and observer-dependent visual scoring of immunohistochemistry.

SUBMITTER: Gevaert T

PROVIDER: S-EPMC6156570 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores.

Gevaert Thomas T Van Eycke Yves-Rémi YR Vanden Broeck Thomas T Van Poppel Hein H Salmon Isabelle I Rorive Sandrine S Claessens Frank F De Ridder Dirk D Decaestecker Christine C Joniau Steven S

Scientific reports 20180925 1

The recent developments in anti-angiogenic and immunomodulatory drugs show that the tumour micro-environment (TME) becomes increasingly important in cancer research. Here we investigated the correlation between the Gleason score (GS) and the TME by comparing tissue expression profiles of steroid hormone receptors, cancer activated fibroblast (CAF) markers and vessel densities between different GS groups. Therefore, matched patient cohorts were composed for different GS (6-7-8). Tissue micro-arra ...[more]

PMID: 30254333

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Project description:BackgroundAlthough prostate cancer (PCa) is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies, or differences in lifestyle. Gut microbiota has recently been associated with cancer progression, but its role in PCa is unclear.ObjectiveCharacterization of the gut microbiota and its functions associated with PCa.Design setting and participantsIn a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing.Outcome measurements and statistical analysisSequences were assigned to operational taxonomic units, differential abundance analysis, and α- and β-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated.Results and limitationsOf 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level.ConclusionsGut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence.Patient summaryIn this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.

Project description:Most proteins are regulated by physical interactions with other molecules; some are highly specific, but others interact with many partners. Despite much speculation, we know little about how and why specificity/promiscuity evolves in natural proteins. It is widely assumed that specific proteins evolved from more promiscuous ancient forms and that most proteins' specificity has been tuned to an optimal state by selection. Here we use ancestral protein reconstruction to trace the evolutionary history of ligand recognition in the steroid hormone receptors (SRs), a family of hormone-regulated animal transcription factors. We resurrected the deepest ancestral proteins in the SR family and characterized the structure-activity relationships by which they distinguished among ligands. We found that that the most ancient split in SR evolution involved a discrete switch from an ancient receptor for aromatized estrogens--including xenobiotics--to a derived receptor that recognized non-aromatized progestagens and corticosteroids. The family's history, viewed in relation to the evolution of their ligands, suggests that SRs evolved according to a principle of minimal specificity: at each point in time, receptors evolved ligand recognition criteria that were just specific enough to parse the set of endogenous substances to which they were exposed. By studying the atomic structures of resurrected SR proteins, we found that their promiscuity evolved because the ancestral binding cavity was larger than the primary ligand and contained excess hydrogen bonding capacity, allowing adventitious recognition of larger molecules with additional functional groups. Our findings provide an historical explanation for the sensitivity of modern SRs to natural and synthetic ligands--including endocrine-disrupting drugs and pollutants--and show that knowledge of history can contribute to ligand prediction. They suggest that SR promiscuity may reflect the limited power of selection within real biological systems to discriminate between perfect and "good enough."

Dataset Information

Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores.

Publications

Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores.

Similar Datasets

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