File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The oxford classic links epithelial-to-mesenchymal transition to immunosuppression in poor prognosis ovarian cancers

TitleThe oxford classic links epithelial-to-mesenchymal transition to immunosuppression in poor prognosis ovarian cancers
Authors
Issue Date2021
Citation
Clinical Cancer Research, 2021, v. 27, n. 5, p. 1570-1579 How to Cite?
AbstractPurpose: Using RNA sequencing, we recently developed the 52-gene-based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. Experimental Design: We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n ¼ 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs. Results: We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition-high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P ¼ 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors. Conclusions: The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.
Persistent Identifierhttp://hdl.handle.net/10722/341505
ISSN
2023 Impact Factor: 10.0
2023 SCImago Journal Rankings: 4.623
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, Zhiyuan-
dc.contributor.authorCunnea, Paula-
dc.contributor.authorZhong, Zhe-
dc.contributor.authorLu, Haonan-
dc.contributor.authorOsagie, Oloruntoba I.-
dc.contributor.authorCampo, Leticia-
dc.contributor.authorArtibani, Mara-
dc.contributor.authorNixon, Katherine-
dc.contributor.authorPloski, Jennifer-
dc.contributor.authorGonzalez, Laura Santana-
dc.contributor.authorAlsaadi, Abdulkhaliq-
dc.contributor.authorWietek, Nina-
dc.contributor.authorDamato, Stephen-
dc.contributor.authorDhar, Sunanda-
dc.contributor.authorBlagden, Sarah P.-
dc.contributor.authorYau, Christopher-
dc.contributor.authorHester, Joanna-
dc.contributor.authorAlbukhari, Ashwag-
dc.contributor.authorAboagye, Eric O.-
dc.contributor.authorFotopoulou, Christina-
dc.contributor.authorAhmed, Ahmed-
dc.date.accessioned2024-03-13T08:43:19Z-
dc.date.available2024-03-13T08:43:19Z-
dc.date.issued2021-
dc.identifier.citationClinical Cancer Research, 2021, v. 27, n. 5, p. 1570-1579-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/341505-
dc.description.abstractPurpose: Using RNA sequencing, we recently developed the 52-gene-based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. Experimental Design: We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n ¼ 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs. Results: We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition-high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P ¼ 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors. Conclusions: The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.-
dc.languageeng-
dc.relation.ispartofClinical Cancer Research-
dc.titleThe oxford classic links epithelial-to-mesenchymal transition to immunosuppression in poor prognosis ovarian cancers-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-20-2782-
dc.identifier.pmid33446563-
dc.identifier.scopuseid_2-s2.0-85102318668-
dc.identifier.volume27-
dc.identifier.issue5-
dc.identifier.spage1570-
dc.identifier.epage1579-
dc.identifier.eissn1557-3265-
dc.identifier.isiWOS:000625367700035-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats