Journal Article

DKFZ-2025-01915

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Transcriptome Analysis of Matched Cohorts of Long- and Short-term Survivors in Advanced High-grade Serous Tubo-ovarian Cancer.

Marchenko, S. ; Goernitz, N. ; Zoern, W. A. ; Joosten, M. ; Hoffmann, I. ; Sehouli, J. ; Niedobitek, G. ; Denkert, C. ; Sinn, B. V. ; Kolb, S. ; Carbonell-Caballero, J. ; Valencia, A. ; Dragomir, M.-P.DKFZ* ; Schmitt, W. D. ; Horst, D. ; Braicu, I. I. ; Sers, C. ; Pohl, J. ; Taube, E. T.

2025
AACR Philadelphia, Pa. [u.a.]

Abstract: The late-stage diagnosis and the aggressiveness of high-grade serous tubo-ovarian carcinoma (HGSC) often result in poor survival outcomes, yet some patients exhibit an exceptionally long survival rate. This study aimed to identify molecular profiles associated with long-/short-term survival in HGSC, with the goal of better understanding protective factors and developing new treatments.To discover molecular drivers causing the aggressiveness of HGSC, tumor samples from 12 long-term HGSC survivors (>7 years overall survival) and 12 short-term survivors (<1 year overall survival) were analyzed using targeted RNA sequencing followed by computational analysis. We investigated differentially expressed genes and their functional relevance, inferred differences in cell type composition and signaling pathways, as well as mutation status. To validate our findings, we simulated our study design by using HGSC The Cancer Genome Atlas dataset samples. We evaluated differential patterns of gene expression between these two groups and developed molecular profiles of HGSC that correlate with survival phenotypes.Besides known molecular cancer drivers and indicators of poor prognosis, we identified specific transcriptional changes between short- and long-term survivors of HGSC, which indicate that immune processes play a fundamental role in long-term survivors. Our computational analysis reveals an important role for the ensemble of IFN-γ signaling and the RFX transcription factors, as well as the immune cell composition of the tumor microenvironment.Specific immunologic requirements involving IFN-γ signaling and affected pathways seem to be relevant for long-term survival in the generally considered nonimmunogenic HGSC, necessitating further research to improve diagnostic strategies and targeted therapies.

Keyword(s): Humans (MeSH) ; Female (MeSH) ; Ovarian Neoplasms: genetics (MeSH) ; Ovarian Neoplasms: mortality (MeSH) ; Ovarian Neoplasms: pathology (MeSH) ; Gene Expression Profiling (MeSH) ; Cancer Survivors (MeSH) ; Transcriptome (MeSH) ; Prognosis (MeSH) ; Cystadenocarcinoma, Serous: genetics (MeSH) ; Cystadenocarcinoma, Serous: pathology (MeSH) ; Cystadenocarcinoma, Serous: mortality (MeSH) ; Gene Expression Regulation, Neoplastic (MeSH) ; Middle Aged (MeSH) ; Biomarkers, Tumor: genetics (MeSH) ; Aged (MeSH) ; Neoplasm Grading (MeSH) ; Biomarkers, Tumor

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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