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Gene expression pro...
Gene expression profiles define molecular subtypes of prostate cancer bone metastases with different outcomes and morphology traceable back to the primary tumor
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- Thysell, Elin (författare)
- Umeå universitet,Patologi,Umea Univ, Dept Med Biosci, Pathol, SE-90185 Umea, Sweden
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- Vidman, Linda (författare)
- Umeå universitet,Institutionen för matematik och matematisk statistik,Umea Univ, Dept Math & Math Stat, Umea, Sweden
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- Bovinder Ylitalo, Erik (författare)
- Umeå universitet,Patologi,Umea Univ, Dept Med Biosci, Pathol, SE-90185 Umea, Sweden
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- Jernberg, Emma (författare)
- Umeå universitet,Patologi,Umea Univ, Dept Med Biosci, Pathol, SE-90185 Umea, Sweden
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- Crnalic, Sead (författare)
- Umeå universitet,Ortopedi,Umea Univ, Dept Surg & Perioperat Sci, Orthopaed, Umea, Sweden
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- Iglesias-Gato, Diego (författare)
- Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark
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- Flores-Morales, Amilcar (författare)
- Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark
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- Stattin, Pär (författare)
- Uppsala universitet,Umeå universitet,Urologi och andrologi,Urologkirurgi
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- Egevad, Lars (författare)
- Karolinska Institutet
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- Widmark, Anders (författare)
- Umeå universitet,Onkologi,Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden
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- Rydén, Patrik (författare)
- Umeå universitet,Institutionen för matematik och matematisk statistik,Umea Univ, Dept Math & Math Stat, Umea, Sweden
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- Bergh, Anders (författare)
- Umeå universitet,Patologi,Umea Univ, Dept Med Biosci, Pathol, SE-90185 Umea, Sweden
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- Wikström, Pernilla (författare)
- Umeå universitet,Patologi,Umea Univ, Dept Med Biosci, Pathol, SE-90185 Umea, Sweden
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(creator_code:org_t)
- 2019-06-27
- 2019
- Engelska.
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Ingår i: Molecular Oncology. - : John Wiley & Sons. - 1574-7891 .- 1878-0261. ; 13:8, s. 1763-1777
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://febs.onlinel...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Bone metastasis is the lethal end-stage of prostate cancer (PC), but the biology of bone metastases is poorly understood. The overall aim of this study was therefore to explore molecular variability in PC bone metastases of potential importance for therapy. Specifically, genome-wide expression profiles of bone metastases from untreated patients (n = 12) and patients treated with androgen-deprivation therapy (ADT, n = 60) were analyzed in relation to patient outcome and to morphological characteristics in metastases and paired primary tumors. Principal component analysis and unsupervised classification were used to identify sample clusters based on mRNA profiles. Clusters were characterized by gene set enrichment analysis and related to histological and clinical parameters using univariate and multivariate statistics. Selected proteins were analyzed by immunohistochemistry in metastases and matched primary tumors (n = 52) and in transurethral resected prostate (TUR-P) tissue of a separate cohort (n = 59). Three molecular subtypes of bone metastases (MetA-C) characterized by differences in gene expression pattern, morphology, and clinical behavior were identified. MetA (71% of the cases) showed increased expression of androgen receptor-regulated genes, including prostate-specific antigen (PSA), and glandular structures indicating a luminal cell phenotype. MetB (17%) showed expression profiles related to cell cycle activity and DNA damage, and a pronounced cellular atypia. MetC (12%) exhibited enriched stroma-epithelial cell interactions. MetB patients had the lowest serum PSA levels and the poorest prognosis after ADT. Combined analysis of PSA and Ki67 immunoreactivity (proliferation) in bone metastases, paired primary tumors, and TUR-P samples was able to differentiate MetA-like (high PSA, low Ki67) from MetB-like (low PSA, high Ki67) tumors and demonstrate their different prognosis. In conclusion, bone metastases from PC patients are separated based on gene expression profiles into molecular subtypes with different morphology, biology, and clinical outcome. These findings deserve further exploration with the purpose of improving treatment of metastatic PC.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- bone metastasis
- gene expression
- gene set enrichment analysis
- morphology
- survival
- unsupervised cluster analysis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Thysell, Elin
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Vidman, Linda
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Bovinder Ylitalo ...
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Jernberg, Emma
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Crnalic, Sead
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Iglesias-Gato, D ...
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visa fler...
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Flores-Morales, ...
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Stattin, Pär
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Egevad, Lars
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Widmark, Anders
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Rydén, Patrik
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Bergh, Anders
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Wikström, Pernil ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Molecular Oncolo ...
- Av lärosätet
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Umeå universitet
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Uppsala universitet
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Karolinska Institutet