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

TitleAPOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis.
Authors
Issue Date30-Jun-2023
PublisherSpringer Nature [academic journals on nature.com]
Citation
British Journal of Cancer, 2023, v. 128, n. 11, p. 2054-2062 How to Cite?
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.


Persistent Identifierhttp://hdl.handle.net/10722/329044
ISSN
2023 Impact Factor: 6.4
2023 SCImago Journal Rankings: 3.000
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLong, XR-
dc.contributor.authorLu, HW-
dc.contributor.authorCai, MC-
dc.contributor.authorZang, JY-
dc.contributor.authorZhang, ZQ-
dc.contributor.authorWu, J-
dc.contributor.authorLiu, XS-
dc.contributor.authorCheng, L-
dc.contributor.authorCheng, JJ-
dc.contributor.authorCheung, LWT-
dc.contributor.authorShen, Z-
dc.contributor.authorZhou, Y-
dc.contributor.authorDi, W-
dc.contributor.authorZhuang, GL-
dc.contributor.authorYin, X -
dc.date.accessioned2023-08-05T07:54:51Z-
dc.date.available2023-08-05T07:54:51Z-
dc.date.issued2023-06-30-
dc.identifier.citationBritish Journal of Cancer, 2023, v. 128, n. 11, p. 2054-2062-
dc.identifier.issn0007-0920-
dc.identifier.urihttp://hdl.handle.net/10722/329044-
dc.description.abstract<h3>Background</h3><p>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.</p><h3>Methods</h3><p>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.</p><h3>Results</h3><p>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.</p><h3>Conclusions</h3><p>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.</p>-
dc.languageeng-
dc.publisherSpringer Nature [academic journals on nature.com]-
dc.relation.ispartofBritish Journal of Cancer-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleAPOBEC3B stratifies ovarian clear cell carcinoma with distinct immunophenotype and prognosis.-
dc.typeArticle-
dc.identifier.doi10.1038/s41416-023-02239-5-
dc.identifier.pmid36997661-
dc.identifier.scopuseid_2-s2.0-85151386764-
dc.identifier.volume128-
dc.identifier.issue11-
dc.identifier.spage2054-
dc.identifier.epage2062-
dc.identifier.eissn1532-1827-
dc.identifier.isiWOS:000960847900001-
dc.identifier.issnl0007-0920-

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