Prognostic relevance of HRDness gene expression signature in ovarian high-grade serous carcinoma; JGOG3025-TR2 study

Shiro Takamatsu, Kosuke Yoshihara, Tsukasa Baba, Muneaki Shimada, Hiroshi Yoshida, Hiroaki Kajiyama, Katsutoshi Oda, Masaki Mandai, Aikou Okamoto, Takayuki Enomoto, Noriomi Matsumura

Research output: Contribution to journalArticlepeer-review


Background: This study aimed to evaluate the homologous recombination repair pathway deficiency (HRD) in ovarian high-grade serous carcinoma (HGSC). Methods: In the ovarian cancer data from The Cancer Genome Atlas, we identified genes differentially expressed between tumours with and without HRD genomic scars and named these genes “HRDness signature”. We performed SNP array, RNA sequencing, and methylation array analyses on 274 HGSC tumours for which targeted sequencing of 51 genes and clinical data were available to generate JGOG3025-TR2 dataset. The HRDness signature was tested on external datasets, including the JGOG3025-TR2 cohort, by computational scoring and machine-learning prediction. Results: High scores and positive predictions of the HRDness signature were significantly associated with BRCA alterations, genomic scar scores, and better survival. On the other hand, among cases with high scores and/or positive predictions, those with BRCA1 methylation showed poorer survival. In the JGOG3025-TR2 cohort, HRD status was significantly associated with the use of olaparib after relapse and progression-free survival after its initiation. Conclusions: The HRDness gene expression signature is associated with a good prognosis, while BRCA1 methylation is associated with a poor prognosis. The newly generated JGOG3025-TR2 dataset will be useful in future HGSC studies.

Original languageEnglish
Pages (from-to)1095-1104
Number of pages10
JournalBritish Journal of Cancer
Issue number6
Publication statusAccepted/In press - 2023
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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