Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease
<p><strong>Purpose</strong> It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies fro...
| मुख्य लेखकों: | , , , , , , , , , , |
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| स्वरूप: | Internet publication |
| भाषा: | English |
| प्रकाशित: |
2023
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| _version_ | 1826312763630157824 |
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| author | Charlton, P O’Reilly, D Philippou, Y Rao, SR Lamb, AD Mills, IG Higgins, G Hamdy, FC Verrill, C Buffa, FM Bryant, RJ |
| author_facet | Charlton, P O’Reilly, D Philippou, Y Rao, SR Lamb, AD Mills, IG Higgins, G Hamdy, FC Verrill, C Buffa, FM Bryant, RJ |
| author_sort | Charlton, P |
| collection | OXFORD |
| description | <p><strong>Purpose</strong> It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with i) stable PCa post-primary or salvage RT (sPCa), ii) progressing PCa post-RT (pPCa), and iii) <i>de novo</i> metastatic PCa (mPCa).</p>
<p><strong>Experimental Design</strong> A cohort of 19 patients with diagnostic prostate biopsies (n=6 sPCa, n=5 pPCa, n=8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009-2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3’RNA sequencing (3’RNAseq) (n=19), nanoString analysis (n=12) and Illumina 850k methylation (n=8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes (DEGs) and methylated genomic regions (MGRs).</p>
<p><strong>Results</strong> 18 of 19 samples provided useable 3’RNAseq data. Principal Component Analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ∼600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (<i>p</i><0.0001) in an external cohort.</p>
<p><strong>Conclusions</strong> 3’RNAseq, nanoString and 850K-methylation analyses are each achievable from historical FFPE diagnostic pre-treatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation.</p> |
| first_indexed | 2024-04-23T08:25:31Z |
| format | Internet publication |
| id | oxford-uuid:5b726d5b-a085-4420-aa58-e60fb8a8619b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-04-23T08:25:31Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | oxford-uuid:5b726d5b-a085-4420-aa58-e60fb8a8619b2024-04-16T14:29:24ZMolecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic diseaseInternet publicationhttp://purl.org/coar/resource_type/c_7ad9uuid:5b726d5b-a085-4420-aa58-e60fb8a8619bEnglishSymplectic Elements2023Charlton, PO’Reilly, DPhilippou, YRao, SRLamb, ADMills, IGHiggins, GHamdy, FCVerrill, CBuffa, FMBryant, RJ<p><strong>Purpose</strong> It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with i) stable PCa post-primary or salvage RT (sPCa), ii) progressing PCa post-RT (pPCa), and iii) <i>de novo</i> metastatic PCa (mPCa).</p> <p><strong>Experimental Design</strong> A cohort of 19 patients with diagnostic prostate biopsies (n=6 sPCa, n=5 pPCa, n=8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009-2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3’RNA sequencing (3’RNAseq) (n=19), nanoString analysis (n=12) and Illumina 850k methylation (n=8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes (DEGs) and methylated genomic regions (MGRs).</p> <p><strong>Results</strong> 18 of 19 samples provided useable 3’RNAseq data. Principal Component Analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ∼600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (<i>p</i><0.0001) in an external cohort.</p> <p><strong>Conclusions</strong> 3’RNAseq, nanoString and 850K-methylation analyses are each achievable from historical FFPE diagnostic pre-treatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation.</p> |
| spellingShingle | Charlton, P O’Reilly, D Philippou, Y Rao, SR Lamb, AD Mills, IG Higgins, G Hamdy, FC Verrill, C Buffa, FM Bryant, RJ Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease |
| title | Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease |
| title_full | Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease |
| title_fullStr | Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease |
| title_full_unstemmed | Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease |
| title_short | Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease |
| title_sort | molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post radiotherapy and those with de novo metastatic disease |
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