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- Title
A prognostic hypoxia gene signature with low heterogeneity within the dominant tumour lesion in prostate cancer patients.
- Authors
Salberg, Unn Beate; Skingen, Vilde Eide; Fjeldbo, Christina Sæten; Hompland, Tord; Ragnum, Harald Bull; Vlatkovic, Ljiljana; Hole, Knut Håkon; Seierstad, Therese; Lyng, Heidi
- Abstract
<bold>Background: </bold>Gene signatures measured in a biopsy have been proposed as hypoxia biomarkers in prostate cancer. We assessed a previously developed signature, and aimed to determine its relationship to hypoxia and its heterogeneity within the dominant (index) lesion of prostate cancer.<bold>Methods: </bold>The 32-gene signature was assessed from gene expression data of 141 biopsies from the index lesion of 94 patients treated with prostatectomy. A gene score calculated from the expression levels was applied in the analyses. Hypoxic fraction from pimonidazole immunostained whole-mount and biopsy sections was used as reference standard for hypoxia.<bold>Results: </bold>The gene score was correlated with pimonidazole-defined hypoxic fraction in whole-mount sections, and the two parameters showed almost equal association with clinical markers of tumour aggressiveness. Based on the gene score, incorrect classification according to hypoxic fraction in whole-mount sections was seen in one third of the patients. The incorrect classifications were apparently not due to intra-tumour heterogeneity, since the score had low heterogeneity compared to pimonidazole-defined hypoxic fraction in biopsies. The score showed prognostic significance in uni-and multivariate analysis in independent cohorts.<bold>Conclusions: </bold>Our signature from the index lesion reflects tumour hypoxia and predicts prognosis in prostate cancer, independent of intra-tumour heterogeneity in pimonidazole-defined hypoxia.
- Publication
British Journal of Cancer, 2022, Vol 127, Issue 2, p321
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-022-01782-x