ArticleBritish journal of cancer2022
Upregulation of CXCL1 and LY9 contributes to BRCAness in ovarian cancer and mediates response to PARPi and immune checkpoint blockade.
Article in British journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy.Molecular cancer · 2025Review
- Individualized diagnosis of rheumatoid arthritis: A rank-based qualitative T cell-related signature.PloS one · 2025Article
- Individualized detection of TMPRSS2-ERG fusion status in prostate cancer: a rank-based qualitative transcriptome signature.World journal of surgical oncology · 2024Article
- Signaling lymphocytic activation molecule family receptors as potential immune therapeutic targets in solid tumors.Frontiers in immunology · 2024Review
- Integrated immunogenomic analyses of high-grade serous ovarian cancer reveal vulnerability to combination immunotherapy.Frontiers in immunology · 2024Article
- Proteome-Wide Mendelian Randomization Analysis to Identify Potential Plasma Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer Subtypes.International journal of women's health · 2024Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in BRCA1 or BRCA2 (BRCA1/2) cause homologous recombination deficiency (HRD). Ovarian cancer (OvCa) patients harbouring HRD beyond BRCA1/2 mutation result in a state referred to as "BRCAness". OvCa with BRCAness could benefit from PARP inhibitors. This study aims to identify a signature to detect the BRCAness population at the transcriptome level.
methodsWe used a rank-based algorithm to develop a qualitative BRCAness signature for OvCa. Upregulation of CXCL1 with downregulation of SV2A and upregulation of LY9 with downregulation of CHRNB3 were constructed as the BRCAness signature (2 gene pairs, 2-GPS) for OvCa.
resultsOvCa samples that were classified as BRCAness by 2-GPS showed improved overall survival, progression-free survival and exhibited increased multi-omics alterations in homologous recombination genes and enhanced sensitivity to immune checkpoint blockade. BRCAness cells were sensitive to PARP inhibitors. By biological experiments, we validated SKOV3 cells and patients with HRD exhibited higher expression of CXCL1 than SV2A and higher expression of LY9 than CHRNB3 at mRNA level. Both SKOV3 and A2780 with HRD were sensitive to mitomycin C, cisplatin and olaparib.
conclusionsIn conclusion, 2-GPS could robustly predict BRCAness OvCa at the individual level and extend the population who may benefit from PARP inhibitors.
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