Evidence map›Paper›PMID 39217197›Full record

ArticleScientific reports2024

Digital spatial profiling identifies the tumor center as a topological niche in prostate cancer characterized by an upregulation of BAD.

Ann-Kathrin Huber, Adam Kaczorowski, Felix Schneider, Sarah Böning, Magdalena Görtz, David Langhoff, Constantin Schwab, Albrecht Stenzinger, Markus Hohenfellner, Anette Duensing and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Ann-Kathrin HuberMolecular Urooncology, Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany.
Adam KaczorowskiMolecular Urooncology, Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany.
Felix SchneiderMolecular Urooncology, Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany.
Sarah BöningMolecular Urooncology, Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany.
Magdalena GörtzDepartment of Urology, University Hospital Heidelberg, and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.
David LanghoffMolecular Urooncology, Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany.
Constantin SchwabInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Albrecht StenzingerInstitute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Markus HohenfellnerDepartment of Urology, University Hospital Heidelberg, and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 420, 69120, Heidelberg, Germany.
Anette DuensingPrecision Oncology of Urological Malignancies, Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany.
Stefan DuensingMolecular Urooncology, Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany. stefan.duensing@med.uni-heidelberg.de.

Funding

German Federal Ministry for Economic Affairs and Climate Action 01MT21004A
6 · The paper itself

Abstract

Prostate cancer is characterized by a high degree of intratumoral heterogeneity. However, little is known about the spatial distribution of cancer cells with respect to specific functional characteristics and the formation of spatial niches. Here, we used digital spatial profiling (DSP) to investigate differences in protein expression in the tumor center versus the tumor periphery. Thirty-seven regions of interest were analyzed for the expression of 47 proteins, which included components of the PI3K-AKT, MAPK, and cell death signaling pathways as well as immune cell markers. A total of 1739 data points were collected from five patients. DSP identified the BCL-2 associated agonist of cell death (BAD) protein as the most significantly upregulated protein in the tumor center. BAD upregulation was confirmed by conventional immunohistochemistry, which furthermore showed a phosphorylation of BAD at serine 112 indicating its inactivation. Knockdown of BAD in prostate cancer cells in vitro led to decreased cell viability and colony growth. Clinically, high BAD expression was associated with a shorter time to biochemical recurrence in 158 mostly high-risk prostate cancer patients. Collectively, our results suggest that the tumor center is a topological niche with high BAD expression that may drive prostate cancer progression.

Indexed as

bcl-Associated Death ProteinProstatic NeoplasmsUp-RegulationAgedBiomarkers, TumorCell Line, TumorGene Expression Regulation, NeoplasticHumansMaleMiddle AgedPhosphorylationSignal TransductionTumor MicroenvironmentBAD protein, humanbcl-Associated Death ProteinBiomarkers, TumorBADIntratumoral heterogeneityProstate cancerSpatial biologyTumor center

Identifiers

PMID39217197
PMCPMC11366015

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.