Communications biology · 2025
Long non-coding RNAs as a biomarker for homologous recombination deficiency and parp inhibitor sensitivity in high-grade serous ovarian cancers.
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Doberstein Kai, Panther Johannes, Hahnen Eric, Richters Lisa, Schouten Philip C, Harter Philipp, Heitz Florian, Kommoss Stefan, Berlit Sebastian, Tuschy Benjamin, Sütterlin Marc, Marmé Frederik
Аннотация
Homologous recombination deficiency (HRD) and sensitivity to PARP inhibitors are key determinants of therapeutic response in high-grade serous ovarian cancer (HGSC), yet predictive biomarkers beyond BRCA1/2 mutations or genomic HRD scores remain inadequate. Here, we investigate the potential of long non-coding RNAs (lncRNAs) as predictive markers of HRD and PARP inhibitor response. We identify a panel of lncRNAs that stratifies HGSC tumors by HRD status and drug sensitivity. Among these, ENSG00000272172.1 is significantly upregulated in HRD-positive tumors and is detectable in both formalin-fixed tissue and plasma, supporting its use as a minimally invasive biomarker. Functional analyses reveal that this lncRNA contributes to genome stability by modulating replication dynamics. These findings highlight a previously unrecognized role for lncRNAs in the HRD phenotype and suggest translational potential for ENSG00000272172.1 in guiding clinical decision-making.