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...
| मुख्य लेखकों: | , , , , , , , , , , , , , , , , , , , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
BioMed Central
2023
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| _version_ | 1826311508810792960 |
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| author | Figiel, S Yin, W Doultsinos, D Erickson, A Poulose, N Singh, R Magnussen, A Anbarasan, T Teague, R He, M Lundeberg, J Loda, M Verrill, C Colling, R Gill, PS Bryant, RJ Hamdy, FC Woodcock, DJ Mills, IG Cussenot, O Lamb, AD |
| author_facet | Figiel, S Yin, W Doultsinos, D Erickson, A Poulose, N Singh, R Magnussen, A Anbarasan, T Teague, R He, M Lundeberg, J Loda, M Verrill, C Colling, R Gill, PS Bryant, RJ Hamdy, FC Woodcock, DJ Mills, IG Cussenot, O Lamb, AD |
| author_sort | Figiel, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T08:10:54Z |
| format | Journal article |
| id | oxford-uuid:48d3b8b2-e02c-48ba-97b6-d3301a07a22f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:10:54Z |
| publishDate | 2023 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:48d3b8b2-e02c-48ba-97b6-d3301a07a22f2023-11-28T15:19:11ZSpatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signaturesJournal articlehttp://purl.org/coar/resource_type/c_1843uuid:48d3b8b2-e02c-48ba-97b6-d3301a07a22fEnglishSymplectic ElementsBioMed Central2023Figiel, SYin, WDoultsinos, DErickson, APoulose, NSingh, RMagnussen, AAnbarasan, TTeague, RHe, MLundeberg, JLoda, MVerrill, CColling, RGill, PSBryant, RJHamdy, FCWoodcock, DJMills, IGCussenot, OLamb, ADGenetic 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. |
| spellingShingle | Figiel, S Yin, W Doultsinos, D Erickson, A Poulose, N Singh, R Magnussen, A Anbarasan, T Teague, R He, M Lundeberg, J Loda, M Verrill, C Colling, R Gill, PS Bryant, RJ Hamdy, FC Woodcock, DJ Mills, IG Cussenot, O Lamb, AD Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures |
| title | Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures |
| title_full | Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures |
| title_fullStr | Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures |
| title_full_unstemmed | Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures |
| title_short | Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures |
| title_sort | spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures |
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