Marianne Bjerre

Epigenetic silencing of MEIS2 in prostate cancer recurrence

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Epigenetic silencing of MEIS2 in prostate cancer recurrence. / Nørgaard, Maibritt; Haldrup, Christa; Bjerre, Marianne Trier et al.

In: Clinical Epigenetics, Vol. 11, No. 1, 147, 22.10.2019, p. 147.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Nørgaard, M, Haldrup, C, Bjerre, MT, Høyer, S, Ulhøi, B, Borre, M & Sørensen, KD 2019, 'Epigenetic silencing of MEIS2 in prostate cancer recurrence', Clinical Epigenetics, vol. 11, no. 1, 147, pp. 147. https://doi.org/10.1186/s13148-019-0742-x

APA

Nørgaard, M., Haldrup, C., Bjerre, M. T., Høyer, S., Ulhøi, B., Borre, M., & Sørensen, K. D. (2019). Epigenetic silencing of MEIS2 in prostate cancer recurrence. Clinical Epigenetics, 11(1), 147. [147]. https://doi.org/10.1186/s13148-019-0742-x

CBE

MLA

Nørgaard, Maibritt et al. "Epigenetic silencing of MEIS2 in prostate cancer recurrence". Clinical Epigenetics. 2019, 11(1). 147. https://doi.org/10.1186/s13148-019-0742-x

Vancouver

Nørgaard M, Haldrup C, Bjerre MT, Høyer S, Ulhøi B, Borre M et al. Epigenetic silencing of MEIS2 in prostate cancer recurrence. Clinical Epigenetics. 2019 Oct 22;11(1):147. 147. doi: 10.1186/s13148-019-0742-x

Author

Nørgaard, Maibritt ; Haldrup, Christa ; Bjerre, Marianne Trier et al. / Epigenetic silencing of MEIS2 in prostate cancer recurrence. In: Clinical Epigenetics. 2019 ; Vol. 11, No. 1. pp. 147.

Bibtex

@article{b791b889eb834606ace9092d14ecc62b,
title = "Epigenetic silencing of MEIS2 in prostate cancer recurrence",
abstract = "BACKGROUND: Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, resulting in overdiagnosis and overtreatment of clinically insignificant tumors. Thus, to improve the management of PC, novel biomarkers are urgently needed.RESULTS: In this study, we integrated genome-wide methylome (Illumina 450K DNA methylation array (450K)) and RNA sequencing (RNAseq) data performed in a discovery set of 27 PC and 15 adjacent normal (AN) prostate tissue samples to identify candidate driver genes involved in PC development and/or progression. We found significant enrichment for homeobox genes among the most aberrantly methylated and transcriptionally dysregulated genes in PC. Specifically, homeobox gene MEIS2 (Myeloid Ecotropic viral Insertion Site 2) was significantly hypermethylated (p < 0.0001, Mann-Whitney test) and transcriptionally downregulated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue in our discovery sample set, which was also confirmed in an independent validation set including > 500 PC and AN tissue samples in total (TCGA cohort analyzed by 450K and RNAseq). Furthermore, in three independent radical prostatectomy (RP) cohorts (n > 700 patients in total), low MEIS2 transcriptional expression was significantly associated with poor biochemical recurrence (BCR) free survival (p = 0.0084, 0.0001, and 0.0191, respectively; log-rank test). Next, we analyzed another RP cohort consisting of > 200 PC, AN, and benign prostatic hyperplasia (BPH) samples by quantitative methylation-specific PCR (qMSP) and found that MEIS2 was significantly hypermethylated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue samples (AN and BPH) with an AUC > 0.84. Moreover, in this cohort, aberrant MEIS2 hypermethylation was significantly associated with post-operative BCR (p = 0.0068, log-rank test), which was subsequently confirmed (p = 0.0067; log-rank test) in the independent TCGA validation cohort (497 RP patients; 450K data).CONCLUSIONS: To the best of our knowledge, this is the first study to investigate, demonstrate, and independently validate a prognostic biomarker potential for MEIS2 at the transcriptional expression level and at the DNA methylation level in PC.",
keywords = "Biomarker, DNA methylation, Epigenetic silencing, MEIS2, Prognosis, Prostate cancer, RNA expression",
author = "Maibritt N{\o}rgaard and Christa Haldrup and Bjerre, {Marianne Trier} and S{\o}ren H{\o}yer and Benedicte Ulh{\o}i and Michael Borre and S{\o}rensen, {Karina D}",
year = "2019",
month = oct,
day = "22",
doi = "10.1186/s13148-019-0742-x",
language = "English",
volume = "11",
pages = "147",
journal = "Clinical Epigenetics (Print)",
issn = "1868-7075",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Epigenetic silencing of MEIS2 in prostate cancer recurrence

AU - Nørgaard, Maibritt

AU - Haldrup, Christa

AU - Bjerre, Marianne Trier

AU - Høyer, Søren

AU - Ulhøi, Benedicte

AU - Borre, Michael

AU - Sørensen, Karina D

PY - 2019/10/22

Y1 - 2019/10/22

N2 - BACKGROUND: Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, resulting in overdiagnosis and overtreatment of clinically insignificant tumors. Thus, to improve the management of PC, novel biomarkers are urgently needed.RESULTS: In this study, we integrated genome-wide methylome (Illumina 450K DNA methylation array (450K)) and RNA sequencing (RNAseq) data performed in a discovery set of 27 PC and 15 adjacent normal (AN) prostate tissue samples to identify candidate driver genes involved in PC development and/or progression. We found significant enrichment for homeobox genes among the most aberrantly methylated and transcriptionally dysregulated genes in PC. Specifically, homeobox gene MEIS2 (Myeloid Ecotropic viral Insertion Site 2) was significantly hypermethylated (p < 0.0001, Mann-Whitney test) and transcriptionally downregulated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue in our discovery sample set, which was also confirmed in an independent validation set including > 500 PC and AN tissue samples in total (TCGA cohort analyzed by 450K and RNAseq). Furthermore, in three independent radical prostatectomy (RP) cohorts (n > 700 patients in total), low MEIS2 transcriptional expression was significantly associated with poor biochemical recurrence (BCR) free survival (p = 0.0084, 0.0001, and 0.0191, respectively; log-rank test). Next, we analyzed another RP cohort consisting of > 200 PC, AN, and benign prostatic hyperplasia (BPH) samples by quantitative methylation-specific PCR (qMSP) and found that MEIS2 was significantly hypermethylated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue samples (AN and BPH) with an AUC > 0.84. Moreover, in this cohort, aberrant MEIS2 hypermethylation was significantly associated with post-operative BCR (p = 0.0068, log-rank test), which was subsequently confirmed (p = 0.0067; log-rank test) in the independent TCGA validation cohort (497 RP patients; 450K data).CONCLUSIONS: To the best of our knowledge, this is the first study to investigate, demonstrate, and independently validate a prognostic biomarker potential for MEIS2 at the transcriptional expression level and at the DNA methylation level in PC.

AB - BACKGROUND: Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, resulting in overdiagnosis and overtreatment of clinically insignificant tumors. Thus, to improve the management of PC, novel biomarkers are urgently needed.RESULTS: In this study, we integrated genome-wide methylome (Illumina 450K DNA methylation array (450K)) and RNA sequencing (RNAseq) data performed in a discovery set of 27 PC and 15 adjacent normal (AN) prostate tissue samples to identify candidate driver genes involved in PC development and/or progression. We found significant enrichment for homeobox genes among the most aberrantly methylated and transcriptionally dysregulated genes in PC. Specifically, homeobox gene MEIS2 (Myeloid Ecotropic viral Insertion Site 2) was significantly hypermethylated (p < 0.0001, Mann-Whitney test) and transcriptionally downregulated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue in our discovery sample set, which was also confirmed in an independent validation set including > 500 PC and AN tissue samples in total (TCGA cohort analyzed by 450K and RNAseq). Furthermore, in three independent radical prostatectomy (RP) cohorts (n > 700 patients in total), low MEIS2 transcriptional expression was significantly associated with poor biochemical recurrence (BCR) free survival (p = 0.0084, 0.0001, and 0.0191, respectively; log-rank test). Next, we analyzed another RP cohort consisting of > 200 PC, AN, and benign prostatic hyperplasia (BPH) samples by quantitative methylation-specific PCR (qMSP) and found that MEIS2 was significantly hypermethylated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue samples (AN and BPH) with an AUC > 0.84. Moreover, in this cohort, aberrant MEIS2 hypermethylation was significantly associated with post-operative BCR (p = 0.0068, log-rank test), which was subsequently confirmed (p = 0.0067; log-rank test) in the independent TCGA validation cohort (497 RP patients; 450K data).CONCLUSIONS: To the best of our knowledge, this is the first study to investigate, demonstrate, and independently validate a prognostic biomarker potential for MEIS2 at the transcriptional expression level and at the DNA methylation level in PC.

KW - Biomarker

KW - DNA methylation

KW - Epigenetic silencing

KW - MEIS2

KW - Prognosis

KW - Prostate cancer

KW - RNA expression

U2 - 10.1186/s13148-019-0742-x

DO - 10.1186/s13148-019-0742-x

M3 - Journal article

C2 - 31640805

VL - 11

SP - 147

JO - Clinical Epigenetics (Print)

JF - Clinical Epigenetics (Print)

SN - 1868-7075

IS - 1

M1 - 147

ER -