CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo

  1. Oh-Hohenhorst, Su Jung
  2. Tilki, Derya
  3. Ahlers, Ann-Kristin
  4. Suling, Anna
  5. Hahn, Oliver
  6. Tennstedt, Pierre
  7. Matuszcak, Christiane
  8. Maar, Hanna
  9. Labitzky, Vera
  10. Hanika, Sandra
  11. Starzonek, Sarah
  12. Baumgart, Simon
  13. Johnsen, Steven ORCID logo
  14. Kluth, Martina
  15. Sirma, Hüseyin
  16. Simon, Ronald
  17. Sauter, Guido
  18. Huland, Hartwig
  19. Schumacher, Udo
  20. Lange, Tobias ORCID logo

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1000 Titel
  • CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo
1000 Autor/in
  1. Oh-Hohenhorst, Su Jung |
  2. Tilki, Derya |
  3. Ahlers, Ann-Kristin |
  4. Suling, Anna |
  5. Hahn, Oliver |
  6. Tennstedt, Pierre |
  7. Matuszcak, Christiane |
  8. Maar, Hanna |
  9. Labitzky, Vera |
  10. Hanika, Sandra |
  11. Starzonek, Sarah |
  12. Baumgart, Simon |
  13. Johnsen, Steven |
  14. Kluth, Martina |
  15. Sirma, Hüseyin |
  16. Simon, Ronald |
  17. Sauter, Guido |
  18. Huland, Hartwig |
  19. Schumacher, Udo |
  20. Lange, Tobias |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-01-07
1000 Erschienen in
1000 Quellenangabe
  • 29(1):49-61
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41417-020-00288-z |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761572/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The outcome of prostate cancer (PCa) patients is highly variable and depends on whether or not distant metastases occur. Multiple chromosomal deletions have been linked to early tumor marker PSA recurrence (biochemical relapse, BCR) after radical prostatectomy (RP), but their potential role for distant metastasis formation is largely unknown. Here, we specifically analyzed whether deletion of the tumor suppressor CHD1 (5q21) influences the post-surgical risk of distant metastasis and whether CHD1 loss directly contributes to metastasis formation in vivo. By considering >6800 patients we found that the CHD1 deletion negatively influences metastasis-free survival in R0 patients (HR: 2.32; 95% CI: 1.61, 3.33; p < 0.001) independent of preoperative PSA, pT stage, pN status, Gleason Score, and BCR. Moreover, CHD1 deletion predicts shortened BCR-free survival in pT2 patients and cancer-specific survival in all patients. In vivo, CHD1 loss increases spontaneous pulmonary metastasis formation in two distinct PCa models coupled with a higher number of multicellular colonies as compared to single-cell metastases. Transcriptome analyses revealed down-regulation of the PCa-specific metastasis suppressor and TGFβ signaling regulator PMEPA1 after CHD1 depletion in both tested PCa models. CHD1 loss increases the risk of postoperative metastasis in R0-resected PCa patients and promotes spontaneous metastasis formation in vivo.
1000 Sacherschließung
lokal Neoplasm Grading [MeSH]
lokal Humans [MeSH]
lokal Metastasis
lokal Prostate-Specific Antigen [MeSH]
lokal Membrane Proteins [MeSH]
lokal Prostatic Neoplasms/pathology [MeSH]
lokal Genes, Tumor Suppressor [MeSH]
lokal DNA-Binding Proteins/genetics [MeSH]
lokal Prostatic Neoplasms/genetics [MeSH]
lokal DNA Helicases/genetics [MeSH]
lokal Article
lokal Male [MeSH]
lokal Disease-Free Survival [MeSH]
lokal Neoplasm Recurrence, Local [MeSH]
lokal Prostatectomy [MeSH]
lokal Prostatic Neoplasms/surgery [MeSH]
lokal Prostate cancer
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/T2gtSG9oZW5ob3JzdCwgU3UgSnVuZw==|https://frl.publisso.de/adhoc/uri/VGlsa2ksIERlcnlh|https://frl.publisso.de/adhoc/uri/QWhsZXJzLCBBbm4tS3Jpc3Rpbg==|https://frl.publisso.de/adhoc/uri/U3VsaW5nLCBBbm5h|https://frl.publisso.de/adhoc/uri/SGFobiwgT2xpdmVy|https://frl.publisso.de/adhoc/uri/VGVubnN0ZWR0LCBQaWVycmU=|https://frl.publisso.de/adhoc/uri/TWF0dXN6Y2FrLCBDaHJpc3RpYW5l|https://frl.publisso.de/adhoc/uri/TWFhciwgSGFubmE=|https://frl.publisso.de/adhoc/uri/TGFiaXR6a3ksIFZlcmE=|https://frl.publisso.de/adhoc/uri/SGFuaWthLCBTYW5kcmE=|https://frl.publisso.de/adhoc/uri/U3RhcnpvbmVrLCBTYXJhaA==|https://frl.publisso.de/adhoc/uri/QmF1bWdhcnQsIFNpbW9u|https://orcid.org/0000-0003-1198-5805|https://frl.publisso.de/adhoc/uri/S2x1dGgsIE1hcnRpbmE=|https://frl.publisso.de/adhoc/uri/U2lybWEsIEjDvHNleWlu|https://frl.publisso.de/adhoc/uri/U2ltb24sIFJvbmFsZA==|https://frl.publisso.de/adhoc/uri/U2F1dGVyLCBHdWlkbw==|https://frl.publisso.de/adhoc/uri/SHVsYW5kLCBIYXJ0d2ln|https://frl.publisso.de/adhoc/uri/U2NodW1hY2hlciwgVWRv|https://orcid.org/0000-0001-6632-337X
1000 Hinweis
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1000 Erstellt am 2023-04-26T15:59:26.401+0200
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1000 Zuletzt bearbeitet Thu Oct 19 13:32:11 CEST 2023
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