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<p>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.</p>

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Long non-coding RNAs as a biomarker for homologous recombination deficiency and parp inhibitor sensitivity in high-grade serous ovarian cancers

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月1日

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  • Kai Doberstein,
  • Johannes Panther,
  • Eric Hahnen,
  • Lisa Richters,
  • Philip C. Schouten,
  • Philipp Harter,
  • Florian Heitz,
  • Stefan Kommoss,
  • Sebastian Berlit,
  • Benjamin Tuschy,
  • Marc Sütterlin,
  • Frederik Marmé

摘要

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.