Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures

Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate can...

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Vydané v:Molecular cancer Ročník 22; číslo 1; s. 162 - 5
Hlavní autori: Figiel, Sandy, Yin, Wencheng, Doultsinos, Dimitrios, Erickson, Andrew, Poulose, Ninu, Singh, Reema, Magnussen, Anette, Anbarasan, Thineskrishna, Teague, Renuka, He, Mengxiao, Lundeberg, Joakim, Loda, Massimo, Verrill, Clare, Colling, Richard, Gill, Pelvender S., Bryant, Richard J., Hamdy, Freddie C., Woodcock, Dan J., Mills, Ian G., Cussenot, Olivier, Lamb, Alastair D.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London BioMed Central 03.10.2023
BioMed Central Ltd
Springer Nature B.V
BMC
Predmet:
Analysis
Archives & records
Biomedical and Life Sciences
Biomedicine
Biopsy
Cancer Research
Cell cycle
Clinical decision making
Cloning
Correspondence
Decision making
Gene expression
Genes
Genetic research
Genomes
Genomics
Health aspects
Humans
Male
Oncology
Prognostic genetic signatures
Prostate - pathology
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Review boards
Spatial transcriptomics
Stroma
Transcriptome
Transcriptomics
Tumors
Virtual biopsy
Virtual biopsy
Spatial transcriptomics
Prostate cancer
Prognostic genetic signatures
ISSN:1476-4598, 1476-4598
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Popis
Shrnutí:Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.
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ISSN:1476-4598
1476-4598
DOI:10.1186/s12943-023-01863-2