Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis
Magnetic resonance imaging (MRI) is increasingly used to triage patients for prostate biopsy. However, 9% to 24% of clinically significant (cs) prostate cancers (PCas) are not visible in MRI. We aimed to identify histomic and transcriptomic determinants of MRI visibility and their association to met...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Wiley
2023
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| _version_ | 1826312584657108992 |
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| author | Lehto, T-PK Pylväläinen, J Sandeman, K Kenttämies, A Nordling, S Mills, IG Tang, J Mirtti, T Rannikko, A |
| author_facet | Lehto, T-PK Pylväläinen, J Sandeman, K Kenttämies, A Nordling, S Mills, IG Tang, J Mirtti, T Rannikko, A |
| author_sort | Lehto, T-PK |
| collection | OXFORD |
| description | Magnetic resonance imaging (MRI) is increasingly used to triage patients for prostate biopsy. However, 9% to 24% of clinically significant (cs) prostate cancers (PCas) are not visible in MRI. We aimed to identify histomic and transcriptomic determinants of MRI visibility and their association to metastasis, and PCa-specific death (PCSD). We studied 45 radical prostatectomy-treated patients with csPCa (grade group [GG]2-3), including 30 with MRI-visible and 15 with MRI-invisible lesions, and 18 men without PCa. First, histological composition was quantified. Next, transcriptomic profiling was performed using NanoString technology. MRI visibility-associated differentially expressed genes (DEGs) and Reactome pathways were identified. MRI visibility was classified using publicly available genes in MSK-IMPACT and Decipher, Oncotype DX, and Prolaris. Finally, DEGs and clinical parameters were used to classify metastasis and PCSD in an external cohort, which included 76 patients with metastatic GG2-4 PCa, and 84 baseline-matched controls without progression. Luminal area was lower in MRI-visible than invisible lesions and low luminal area was associated with short metastasis-free and PCa-specific survival. We identified 67 DEGs, eight of which were associated with survival. Cell division, inflammation and transcriptional regulation pathways were upregulated in MRI-visible csPCas. Genes in Decipher, Oncotype DX and MSK-IMPACT performed well in classifying MRI visibility (AUC = 0.86-0.94). DEGs improved classification of metastasis (AUC = 0.69) and PCSD (AUC = 0.68) over clinical parameters. Our data reveals that MRI-visible csPCas harbor more aggressive histomic and transcriptomic features than MRI-invisible csPCas. Thus, targeted biopsy of visible lesions may be sufficient for risk stratification in patients with a positive MRI. |
| first_indexed | 2024-03-07T08:10:02Z |
| format | Journal article |
| id | oxford-uuid:b9d05e77-623f-42c3-b124-791e3734fcc7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-04-09T03:57:03Z |
| publishDate | 2023 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:b9d05e77-623f-42c3-b124-791e3734fcc72024-03-20T14:59:05ZHistomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b9d05e77-623f-42c3-b124-791e3734fcc7EnglishSymplectic ElementsWiley2023Lehto, T-PKPylväläinen, JSandeman, KKenttämies, ANordling, SMills, IGTang, JMirtti, TRannikko, AMagnetic resonance imaging (MRI) is increasingly used to triage patients for prostate biopsy. However, 9% to 24% of clinically significant (cs) prostate cancers (PCas) are not visible in MRI. We aimed to identify histomic and transcriptomic determinants of MRI visibility and their association to metastasis, and PCa-specific death (PCSD). We studied 45 radical prostatectomy-treated patients with csPCa (grade group [GG]2-3), including 30 with MRI-visible and 15 with MRI-invisible lesions, and 18 men without PCa. First, histological composition was quantified. Next, transcriptomic profiling was performed using NanoString technology. MRI visibility-associated differentially expressed genes (DEGs) and Reactome pathways were identified. MRI visibility was classified using publicly available genes in MSK-IMPACT and Decipher, Oncotype DX, and Prolaris. Finally, DEGs and clinical parameters were used to classify metastasis and PCSD in an external cohort, which included 76 patients with metastatic GG2-4 PCa, and 84 baseline-matched controls without progression. Luminal area was lower in MRI-visible than invisible lesions and low luminal area was associated with short metastasis-free and PCa-specific survival. We identified 67 DEGs, eight of which were associated with survival. Cell division, inflammation and transcriptional regulation pathways were upregulated in MRI-visible csPCas. Genes in Decipher, Oncotype DX and MSK-IMPACT performed well in classifying MRI visibility (AUC = 0.86-0.94). DEGs improved classification of metastasis (AUC = 0.69) and PCSD (AUC = 0.68) over clinical parameters. Our data reveals that MRI-visible csPCas harbor more aggressive histomic and transcriptomic features than MRI-invisible csPCas. Thus, targeted biopsy of visible lesions may be sufficient for risk stratification in patients with a positive MRI. |
| spellingShingle | Lehto, T-PK Pylväläinen, J Sandeman, K Kenttämies, A Nordling, S Mills, IG Tang, J Mirtti, T Rannikko, A Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis |
| title | Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis |
| title_full | Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis |
| title_fullStr | Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis |
| title_full_unstemmed | Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis |
| title_short | Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis |
| title_sort | histomic and transcriptomic features of mri visible and invisible clinically significant prostate cancers are associated with prognosis |
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