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DNA-methylation and genomic copy number in primary tumors and corresponding lymph node metastases in prostate cancer from patients with low and high Gleason score.
Clin. Transl. Radiat. Oncol. 39:100586 (2023)
Purpose: In prostate cancer, the indication to irradiate the pelvic lymphatic pathways in clinical node-negative patients is solely based on clinical nomograms. To define biological risk patterns of lymphatic spread, we studied DNA-methylation and genomic copy number in primary tumors and corresponding lymph nodes metastases. Methods/Patients: DNA-methylation and genomic copy number profiles of primary tumors (PT) and paired synchronous lymph node metastases (LN) from Gleason Score (GS)-6/7a (n = 20 LN-positive, n = 20 LN-negative) and GS-9/10 patients (LN-positive n = 20) after prostatectomy and lymphonodectomy were analyzed. Results: GS-6/7a pN0 PTs and GS-6/7a pN1 PTs differed in histone H3K27me3/H3K9me3 mediated methylation. PTs compared to LNs, in both, GS-6/7a pN1 and GS-9/10 pN1 patients showed large differences in DNA-methylation mediated by histones H3K4me1/2, in addition to copy number changes of chromosomal regions 11q13.1, 14q11.2 and 15q26.1. Between GS-6/7a pN1 and GS-9/10 pN1 patients, methylation levels differed more when comparing LNs than PTs. 16q21-22.1 was specifically lost in GS-9/10 pN0 PTs. Immune system-related pathways characterized the differences between PTs and LNs in both GS-6/7a pN1 and GS-9/10 pN1 patients. Comparing PTs and LKs between GS-6/7a pN1 and GS-9/10 pN1 patients revealed altered transmembrane and G-protein-coupled receptor signaling. Conclusions: Our data suggest that progression of prostate cancer, including lymphatic spread, is associated with histone-mediated DNA-methylation and we hypothesize a methylation signature predicting lymphatic spread in GS-6/7a patients from primary tumors. Lymphatic spread in GS-6/7a patients, flanked by DNA-methylation and CNA alterations, appears to be more complex than in GS-9/10 patients, in whom the primary tumors already appear to bear lymph node metastasis-enabling alterations.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Dna-methylation ; Prostate Lymphatic Spread ; Signature; Long-term Survival; Radiation-therapy; Androgen Suppression; Pelvic Irradiation; High-risk; Radiotherapy; Neoadjuvant; Adenocarcinoma; Update
Language
english
Publication Year
2023
HGF-reported in Year
2023
ISSN (print) / ISBN
2405-6308
e-ISSN
2405-6308
Quellenangaben
Volume: 39,
Article Number: 100586
Publisher
Elsevier
Publishing Place
Amsterdam
Reviewing status
Peer reviewed
Institute(s)
Translational Metabolic Oncology (IDC-TMO)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30203 - Molecular Targets and Therapies
30203 - Molecular Targets and Therapies
Research field(s)
Radiation Sciences
PSP Element(s)
G-521800-001
G-501000-001
G-501000-001
WOS ID
000991804800001
Scopus ID
85146905851
PubMed ID
36935856
Erfassungsdatum
2023-02-04