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. 2017 Apr 12;17(1):261.
doi: 10.1186/s12885-017-3256-y.

Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression

Marjolaine Ngollo  1   2 , Andre Lebert  3 , Marine Daures  1   2 , Gaelle Judes  1   2 , Khaldoun Rifai  1   2 , Lucas Dubois  1   2 , Jean-Louis Kemeny  4 , Frederique Penault-Llorca  2   5 , Yves-Jean Bignon  1   2 , Laurent Guy  2   6 , Dominique Bernard-Gallon  7   8
Affiliations

Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression

Marjolaine Ngollo et al. BMC Cancer. .

Abstract

Background: H3K27me3 histone marks shape the inhibition of gene transcription. In prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate tumor progression.

Methods: We investigated genome-wide H3K27me3 histone methylation profile using chromatin immunoprecipitation (ChIP) and 2X400K promoter microarrays to identify differentially-enriched regions in biopsy samples from prostate cancer patients. H3K27me3 marks were assessed in 34 prostate tumors: 11 with Gleason score > 7 (GS > 7), 10 with Gleason score ≤ 7 (GS ≤ 7), and 13 morphologically normal prostate samples.

Results: Here, H3K27me3 profiling identified an average of 386 enriched-genes on promoter regions in healthy control group versus 545 genes in GS ≤ 7 and 748 genes in GS > 7 group. We then ran a factorial discriminant analysis (FDA) and compared the enriched genes in prostate-tumor biopsies and normal biopsies using ANOVA to identify significantly differentially-enriched genes. The analysis identified ALG5, EXOSC8, CBX1, GRID2, GRIN3B, ING3, MYO1D, NPHP3-AS1, MSH6, FBXO11, SND1, SPATS2, TENM4 and TRA2A genes. These genes are possibly associated with prostate cancer. Notably, the H3K27me3 histone mark emerged as a novel regulatory mechanism in poor-prognosis prostate cancer.

Conclusions: Our findings point to epigenetic mark H3K27me3 as an important event in prostate carcinogenesis and progression. The results reported here provide new molecular insights into the pathogenesis of prostate cancer.

Keywords: Cancer; ChIP-on-chip; Epigenetics; H3K27me3; Histone methylation; Prostate.

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Figures

Fig. 1
Fig. 1
Hierarchical clustering on a set of 13 normal biopsies. The scaled enrichment score of individual patients is plotted in a red-yellow scale. Color intensity reflects magnitude of enrichment score, with red indicating high H3K27me3 enrichment and yellow indicating low H3K27me3 enrichment. Columns represent individual tissues. Rows represent the genes. The dendogram represents overall similarities in patient profiles
Fig. 2
Fig. 2
Hierarchical clustering analysis of tumor tissues with Gleason score ≤ 7. The scaled enrichment score of individual patients is plotted in a red-yellow scale. Color intensity reflects magnitude of enrichment score, with red indicating high H3K27me3 enrichment and yellow indicating low H3K27me3 enrichment. Columns represent individual tissues and rows represent the genes. The dendogram represents overall similarities in patient profiles
Fig. 3
Fig. 3
Hierarchical clustering analyses of patients with Gleason score > 7. The scaled enrichment score of individual patients is plotted in a red-yellow scale. Color intensity reflects magnitude of enrichment score, with red indicating high H3K27me3 enrichment and yellow indicating low H3K27me3 enrichment. Columns represent individual tissues. Rows represent the genes. The dendogram represents overall similarities in patient profiles
Fig. 4
Fig. 4
Factorial discriminant analysis (FDA) of microarray-based genome-wide H3K27me3 profiles derived from prostate biopsies. Prostate biopsies were obtained from healthy patients (n = 13), prostate cancer patients with Gleason score ≤ 7 (n = 10) and prostate cancer patients with Gleason score > 7 (n = 11). Data showed a well-defined separation between patients according to Gleason score and H3K27me3 markers. Center of gravity for each group is reported as the empty symbol. G1, healthy group; G2, prostate cancer with Gleason score ≤ 7; G3 prostate cancer with Gleason score > 7
Fig. 5
Fig. 5
Factorial discriminant analysis. The results represent differentially H3K27me3-enriched genes between prostate cancer tissues versus normal tissues. The Highly enrichment correlated with GS > 7
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