Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis

Timo-Pekka K. Lehto*, Juho Pylväläinen, Kevin Sandeman, Anu Kenttämies, Stig Nordling, Ian G. Mills, Jing Tang, Tuomas Mirtti, Antti Rannikko

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)926-939
Number of pages14
JournalInternational Journal of Cancer
Volume154
Issue number5
Early online date28 Sept 2023
DOIs
Publication statusPublished - 01 Mar 2024

Keywords

  • MSK-IMPACT
  • decipher
  • biomarker
  • Oncotype DX
  • Prolaris

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