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Updated: Dec 29, 2025
Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays
Published on: February 24, 2023
Association between DNA damage repair gene somatic mutations and immune-related gene expression in ovarian cancer
Wenjuan Tian1, Boer Shan1, Yuzi Zhang2
1Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Background:
Defects in DNA damage repair (DDR) system may lead to genomic instability and manifest as increased immunogenicity. DDR deficiency is prevalent in ovarian cancer (OvCa); however, the association of DDR mutation with immune profiles in OvCa remains largely unknown. This knowledge will provide an essential basis to the rational design of biomarker-guided immune combination therapy of OvCa in the future.
Methods:
Whole-exome sequencing data of 587 OvCa from The Cancer Genome Atlas (TCGA) were used to determine the expression profiles of 47 immune-related genes and the abundance of tumor-infiltrating immune cells. A Chinese OvCa cohort (n = 220) tested by next-generation sequencing (NGS) was used to validate the association between DDR status and tumor mutation burden (TMB).
Results:
A total of 19.3% in TCGA cohort and 25.9% in Chinese cohort harbored at least one DDR somatic mutation. DDR deficiency exhibited a distinct immune profile with significant higher expression levels of PTPRCAP, CCL5, IFI16, LAG3, IL15RA, and GBP1 in OvCa in the TCGA cohort. Different DDR pathway deficiency displayed various immune profiles. Increased levels of Th1 cells, TMB, and neoantigen were also observed in DDR-deficient tumors.
Conclusions:
DDR deficiency was associated with specific immune signatures in OvCa. Our findings emphasize the urgent need for biomarker-guided rational immune combination therapy to maximize the OvCa patients who could benefit from immunotherapy.
Insights
DNA damage repair (DDR) defects in ovarian cancer (OvCa) correlate with distinct immune profiles and increased tumor mutation burden. Understanding these associations is key for developing targeted immunotherapies for OvCa patients.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Defects in DNA damage repair (DDR) can cause genomic instability and increase immunogenicity.
- DDR deficiency is common in ovarian cancer (OvCa), but its link to immune profiles is not well understood.
- This knowledge is crucial for designing future biomarker-guided immune combination therapies for OvCa.
Purpose of the Study:
- To investigate the association between DNA damage repair (DDR) mutations and immune profiles in ovarian cancer (OvCa).
- To explore the potential of DDR status as a biomarker for immunotherapy in OvCa.
Main Methods:
- Whole-exome sequencing of 587 OvCa samples from The Cancer Genome Atlas (TCGA).
- Analysis of 47 immune-related genes and tumor-infiltrating immune cells.
- Validation in a Chinese OvCa cohort (n=220) using next-generation sequencing (NGS) to assess DDR status and tumor mutation burden (TMB).
Main Results:
- 19.3% (TCGA) and 25.9% (Chinese cohort) of OvCa harbored DDR somatic mutations.
- DDR deficiency was linked to higher expression of specific immune genes (PTPRCAP, CCL5, IFI16, LAG3, IL15RA, GBP1) and increased Th1 cells, TMB, and neoantigens.
- Different DDR pathways showed distinct immune signatures.
Conclusions:
- DDR deficiency is associated with specific immune signatures in ovarian cancer.
- These findings highlight the need for biomarker-guided immune combination therapies to optimize immunotherapy benefits for OvCa patients.
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