Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C

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Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C

Thysell, Elin (author): Umeå universitet,Patologi

Köhn, Linda, 1979- (author): Umeå universitet,Onkologi

Semenas, Julius (author): Umeå universitet,Patologi

Järemo, Helena (author): Umeå universitet,Patologi

Freyhult, Eva, 1979- (author): Uppsala universitet,Beräkningsbiologi och bioinformatik,Institutionen för medicinska vetenskaper,Science for Life Laboratory, SciLifeLab,National Bioinformatics Infrastructure Sweden

Lundholm, Marie, 1974- (author): Umeå universitet,Patologi

Thellenberg-Karlsson, Camilla, 1972- (author): Umeå universitet,Onkologi

Damber, Jan-Erik, 1949 (author): Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för kliniska vetenskaper, Avdelningen för urologi,Sahlgrenska Center for Cancer Research (SCCR),Institute of Clinical Sciences, Department of Urology

Widmark, Anders (author): Umeå universitet,Onkologi

Crnalic, Sead (author): Umeå universitet,Ortopedi

Josefsson, Andreas, 1979 (author): Umeå universitet,Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för kliniska vetenskaper, Avdelningen för urologi,Sahlgrenska Center for Cancer Research (SCCR),Institute of Clinical Sciences, Department of Urology,Urologi och andrologi,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Department of Urology, Sahlgrenska

Welén, Karin, 1970 (author): Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för urologi,Sahlgrenska Centrum för Cancerforskning (SCCR),Institute of Clinical Sciences, Department of Urology,Sahlgrenska Center for Cancer Research (SCCR)

Nilsson, R. Jonas A. (author): Umeå universitet,Onkologi

Bergh, Anders (author): Umeå universitet,Patologi

Wikström, Pernilla (author): Umeå universitet,Patologi

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2021-12-27
2022
English.
In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 16:4, s. 846-859

Related links:: https://onlinelibrar...; show more...; https://doi.org/10.1...; https://umu.diva-por... (primary) (Raw object); https://uu.diva-port... (primary) (Raw object); https://gup.ub.gu.se...; https://doi.org/10.1...; https://urn.kb.se/re...; https://urn.kb.se/re...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated (n = 21), or castration-resistant (n = 65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples were also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism, and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen receptor-targeting treatments.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

Keyword

MetA-C
metastasis
prognosis
prostate cancer
subtypes
transcriptomic
genomics
Oncology
MetA-C

Publication and Content Type

ref (subject category)
art (subject category)

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By the author/editor: Thysell, Elin; Köhn, Linda, 197 ...; Semenas, Julius; Järemo, Helena; Freyhult, Eva, 1 ...; Lundholm, Marie, ...; show more...; Thellenberg-Karl ...; Damber, Jan-Erik ...; Widmark, Anders; Crnalic, Sead; Josefsson, Andre ...; Welén, Karin, 19 ...; Nilsson, R. Jona ...; Bergh, Anders; Wikström, Pernil ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Urology and Neph ...

Articles in the publication: Molecular Oncolo ...

By the university: University of Gothenburg; Umeå University; Uppsala University

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