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@ARTICLE{Marchenko:304592,
author = {S. Marchenko and N. Goernitz and W. A. Zoern and M. Joosten
and I. Hoffmann and J. Sehouli and G. Niedobitek and C.
Denkert and B. V. Sinn and S. Kolb and J.
Carbonell-Caballero and A. Valencia and M.-P. Dragomir$^*$
and W. D. Schmitt and D. Horst and I. I. Braicu and C. Sers
and J. Pohl and E. T. Taube},
title = {{T}ranscriptome {A}nalysis of {M}atched {C}ohorts of
{L}ong- and {S}hort-term {S}urvivors in {A}dvanced
{H}igh-grade {S}erous {T}ubo-ovarian {C}ancer.},
journal = {Clinical cancer research},
volume = {31},
number = {18},
issn = {1078-0432},
address = {Philadelphia, Pa. [u.a.]},
publisher = {AACR},
reportid = {DKFZ-2025-01915},
pages = {3956 - 3969},
year = {2025},
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.},
keywords = {Humans / Female / Ovarian Neoplasms: genetics / Ovarian
Neoplasms: mortality / Ovarian Neoplasms: pathology / Gene
Expression Profiling / Cancer Survivors / Transcriptome /
Prognosis / Cystadenocarcinoma, Serous: genetics /
Cystadenocarcinoma, Serous: pathology / Cystadenocarcinoma,
Serous: mortality / Gene Expression Regulation, Neoplastic /
Middle Aged / Biomarkers, Tumor: genetics / Aged / Neoplasm
Grading / Biomarkers, Tumor (NLM Chemicals)},
cin = {BE01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40663509},
doi = {10.1158/1078-0432.CCR-24-2794},
url = {https://inrepo02.dkfz.de/record/304592},
}