High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma.
Biomarker
EVI1
HGSOC
Ovarian cancer
PARP
Prognostic biomarker
Journal
Journal of ovarian research
ISSN: 1757-2215
Titre abrégé: J Ovarian Res
Pays: England
ID NLM: 101474849
Informations de publication
Date de publication:
31 Jul 2023
31 Jul 2023
Historique:
received:
23
03
2023
accepted:
16
07
2023
medline:
2
8
2023
pubmed:
1
8
2023
entrez:
31
7
2023
Statut:
epublish
Résumé
Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC. For 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection. High EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504-0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352-0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression. EVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity.
Sections du résumé
BACKGROUND
BACKGROUND
Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC.
METHODS
METHODS
For 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection.
RESULTS
RESULTS
High EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504-0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352-0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression.
CONCLUSIONS
CONCLUSIONS
EVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity.
Identifiants
pubmed: 37525239
doi: 10.1186/s13048-023-01239-6
pii: 10.1186/s13048-023-01239-6
pmc: PMC10388497
doi:
Substances chimiques
MECOM protein, human
0
PARP1 protein, human
EC 2.4.2.30
Biomarkers, Tumor
0
MDS1 and EVI1 Complex Locus Protein
0
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
150Subventions
Organisme : Charité-Universitätsmedizin Berlin and the Berlin Institute of Health
ID : BIH-Charité Junior Clinical Scientist Program
Organisme : Charité-Universitätsmedizin Berlin and the Berlin Institute of Health
ID : BIH-Charité Junior Clinical Scientist Program
Organisme : DKTK Berlin
ID : Young Investigator Grant 2022
Organisme : Berliner Krebsgesellschaft
ID : DRFF202204
Organisme : Transcan
ID : Grant 2014-121
Organisme : Transcan
ID : Grant 2014-121
Informations de copyright
© 2023. The Author(s).
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