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

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CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo. / Oh-Hohenhorst, Su Jung; Tilki, Derya; Ahlers, Ann-Kristin; Suling, Anna; Hahn, Oliver; Tennstedt, Pierre; Matuszcak, Christiane; Maar, Hanna; Labitzky, Vera; Hanika, Sandra; Starzonek, Sarah; Baumgart, Simon; Johnsen, Steven A; Kluth, Martina; Sirma, Hüseyin; Simon, Ronald; Sauter, Guido; Huland, Hartwig; Schumacher, Udo; Lange, Tobias.

In: CANCER GENE THER, Vol. 29, No. 1, 01.2022, p. 49-61.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Oh-Hohenhorst, SJ, Tilki, D, Ahlers, A-K, Suling, A, Hahn, O, Tennstedt, P, Matuszcak, C, Maar, H, Labitzky, V, Hanika, S, Starzonek, S, Baumgart, S, Johnsen, SA, Kluth, M, Sirma, H, Simon, R, Sauter, G, Huland, H, Schumacher, U & Lange, T 2022, 'CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo', CANCER GENE THER, vol. 29, no. 1, pp. 49-61. https://doi.org/10.1038/s41417-020-00288-z

APA

Oh-Hohenhorst, S. J., Tilki, D., Ahlers, A-K., Suling, A., Hahn, O., Tennstedt, P., Matuszcak, C., Maar, H., Labitzky, V., Hanika, S., Starzonek, S., Baumgart, S., Johnsen, S. A., Kluth, M., Sirma, H., Simon, R., Sauter, G., Huland, H., Schumacher, U., & Lange, T. (2022). CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo. CANCER GENE THER, 29(1), 49-61. https://doi.org/10.1038/s41417-020-00288-z

Vancouver

Oh-Hohenhorst SJ, Tilki D, Ahlers A-K, Suling A, Hahn O, Tennstedt P et al. CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo. CANCER GENE THER. 2022 Jan;29(1):49-61. https://doi.org/10.1038/s41417-020-00288-z

Bibtex

@article{48ff099dad724dafb3baa1286b66356e,
title = "CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo",
abstract = "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.",
author = "Oh-Hohenhorst, {Su Jung} and Derya Tilki and Ann-Kristin Ahlers and Anna Suling and Oliver Hahn and Pierre Tennstedt and Christiane Matuszcak and Hanna Maar and Vera Labitzky and Sandra Hanika and Sarah Starzonek and Simon Baumgart and Johnsen, {Steven A} and Martina Kluth and H{\"u}seyin Sirma and Ronald Simon and Guido Sauter and Hartwig Huland and Udo Schumacher and Tobias Lange",
year = "2022",
month = jan,
doi = "10.1038/s41417-020-00288-z",
language = "English",
volume = "29",
pages = "49--61",
journal = "CANCER GENE THER",
issn = "0929-1903",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo

AU - Oh-Hohenhorst, Su Jung

AU - Tilki, Derya

AU - Ahlers, Ann-Kristin

AU - Suling, Anna

AU - Hahn, Oliver

AU - Tennstedt, Pierre

AU - Matuszcak, Christiane

AU - Maar, Hanna

AU - Labitzky, Vera

AU - Hanika, Sandra

AU - Starzonek, Sarah

AU - Baumgart, Simon

AU - Johnsen, Steven A

AU - Kluth, Martina

AU - Sirma, Hüseyin

AU - Simon, Ronald

AU - Sauter, Guido

AU - Huland, Hartwig

AU - Schumacher, Udo

AU - Lange, Tobias

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41417-020-00288-z

DO - 10.1038/s41417-020-00288-z

M3 - SCORING: Journal article

C2 - 33414516

VL - 29

SP - 49

EP - 61

JO - CANCER GENE THER

JF - CANCER GENE THER

SN - 0929-1903

IS - 1

ER -