Related Experiment Video
Updated: Aug 4, 2025
Author Spotlight: Advancing Personalized Medicine in Ovarian Cancer
Published on: February 23, 2024
APOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis
Xiaoran Long1,2, Huaiwu Lu3, Mei-Chun Cai1
1State Key Laboratory of Oncogenes and Related Genes, Department of Obstetrics and Gynecology, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Ovarian clear cell carcinoma (OCCC) is a challenging disease due to its intrinsic chemoresistance. Immunotherapy is an emerging treatment option but currently impeded by insufficient understanding of OCCC immunophenotypes and their molecular determinants.
Methods:
Whole-genome sequencing on 23 pathologically confirmed patients was employed to depict the genomic profile of primary OCCCs. APOBEC3B expression and digital pathology-based Immunoscore were assessed by performing immunohistochemistry and correlated with clinical outcomes.
Results:
An APOBEC-positive (APOBEC+) subtype was identified based on the characteristic mutational signature and prevalent kataegis events. APOBEC + OCCC displayed favourable prognosis across one internal and two external patient cohorts. The improved outcome was ascribable to increased lymphocytic infiltration. Similar phenomena of APOBEC3B expression and T-cell accumulation were observed in endometriotic tissues, suggesting that APOBEC-induced mutagenesis and immunogenicity could occur early during OCCC pathogenesis. Corroborating these results, a case report was presented for an APOBEC + patient demonstrating inflamed tumour microenvironment and clinical response to immune checkpoint blockade.
Conclusions:
Our findings implicate APOBEC3B as a novel mechanism of OCCC stratification with prognostic value and as a potential predictive biomarker that may inform immunotherapeutic opportunities.
