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

Commun Biol. 2025 Oct 1;8(1):1410. doi: 10.1038/s42003-025-08836-9.

Abstract

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.

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Cell Line, Tumor
  • Cystadenocarcinoma, Serous* / drug therapy
  • Cystadenocarcinoma, Serous* / genetics
  • Cystadenocarcinoma, Serous* / pathology
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homologous Recombination*
  • Humans
  • Neoplasm Grading
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors* / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors* / therapeutic use
  • RNA, Long Noncoding* / genetics

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • RNA, Long Noncoding
  • Biomarkers, Tumor