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APOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis.

Authors :
Long, Xiaoran
Lu, Huaiwu
Cai, Mei-Chun
Zang, Jingyu
Zhang, Zhuqing
Wu, Jie
Liu, Xiaoshi
Cheng, Lin
Cheng, Jiejun
Cheung, Lydia W. T.
Shen, Zhen
Zhou, Ying
Di, Wen
Zhuang, Guanglei
Yin, Xia
Source :
British Journal of Cancer; Jun2023, Vol. 128 Issue 11, p2054-2062, 9p
Publication Year :
2023

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00070920
Volume :
128
Issue :
11
Database :
Complementary Index
Journal :
British Journal of Cancer
Publication Type :
Academic Journal
Accession number :
163868786
Full Text :
https://doi.org/10.1038/s41416-023-02239-5