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Identification of biomarkers complementary to homologous recombination deficiency for improving the clinical outcome of ovarian serous cystadenocarcinoma
Ovarian cancer patients with homologous recombination deficiency (HRD) tumors would benefit from PARP inhibitor (PARPi) therapy. However, patients with HRD tumors account for less than 50% of the whole cohort, so new biomarkers still need to be developed. Based on the data from the SNP array and som...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131501/ https://www.ncbi.nlm.nih.gov/pubmed/34047476 http://dx.doi.org/10.1002/ctm2.399 |
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author | Shi, Zhiwen Zhao, Qingguo Lv, Bin Qu, Xinyu Han, Xiao Wang, Hongyan Qiu, Junjun Hua, Keqin |
author_facet | Shi, Zhiwen Zhao, Qingguo Lv, Bin Qu, Xinyu Han, Xiao Wang, Hongyan Qiu, Junjun Hua, Keqin |
author_sort | Shi, Zhiwen |
collection | PubMed |
description | Ovarian cancer patients with homologous recombination deficiency (HRD) tumors would benefit from PARP inhibitor (PARPi) therapy. However, patients with HRD tumors account for less than 50% of the whole cohort, so new biomarkers still need to be developed. Based on the data from the SNP array and somatic mutation profiles in the ovarian cancer genome, we found that high frequency of actionable mutations existed in patients with non‐HRD tumors. Through transcriptome analysis, we identified that a downstream target of the cGAS‐STING pathway, CXCL11, was upregulated in HRD tumors and could be used as a predictor of survival outcome. Further comprehensive analysis of the tumor immune microenvironment (TIME) revealed that CXCL11 expression signature was closely correlated with cytotoxic cells, neoantigen load and immune checkpoint blockade (ICB). Clinical trial data confirmed that the expression of CXCL11 could be used as a biomarker for anti‐PD‐1/PD‐L1 therapy. Finally, in vivo and in vitro experiments showed that cancer cells with PARPi treatment increased the expression of CXCL11. Collectively, our study not only provides biomarkers of ovarian cancer complementary to the HRD score but also introduces a potential new perspective for identifying prognostic biomarkers of immunotherapy. |
format | Online Article Text |
id | pubmed-8131501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81315012021-05-21 Identification of biomarkers complementary to homologous recombination deficiency for improving the clinical outcome of ovarian serous cystadenocarcinoma Shi, Zhiwen Zhao, Qingguo Lv, Bin Qu, Xinyu Han, Xiao Wang, Hongyan Qiu, Junjun Hua, Keqin Clin Transl Med Research Articles Ovarian cancer patients with homologous recombination deficiency (HRD) tumors would benefit from PARP inhibitor (PARPi) therapy. However, patients with HRD tumors account for less than 50% of the whole cohort, so new biomarkers still need to be developed. Based on the data from the SNP array and somatic mutation profiles in the ovarian cancer genome, we found that high frequency of actionable mutations existed in patients with non‐HRD tumors. Through transcriptome analysis, we identified that a downstream target of the cGAS‐STING pathway, CXCL11, was upregulated in HRD tumors and could be used as a predictor of survival outcome. Further comprehensive analysis of the tumor immune microenvironment (TIME) revealed that CXCL11 expression signature was closely correlated with cytotoxic cells, neoantigen load and immune checkpoint blockade (ICB). Clinical trial data confirmed that the expression of CXCL11 could be used as a biomarker for anti‐PD‐1/PD‐L1 therapy. Finally, in vivo and in vitro experiments showed that cancer cells with PARPi treatment increased the expression of CXCL11. Collectively, our study not only provides biomarkers of ovarian cancer complementary to the HRD score but also introduces a potential new perspective for identifying prognostic biomarkers of immunotherapy. John Wiley and Sons Inc. 2021-05-18 /pmc/articles/PMC8131501/ /pubmed/34047476 http://dx.doi.org/10.1002/ctm2.399 Text en © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Shi, Zhiwen Zhao, Qingguo Lv, Bin Qu, Xinyu Han, Xiao Wang, Hongyan Qiu, Junjun Hua, Keqin Identification of biomarkers complementary to homologous recombination deficiency for improving the clinical outcome of ovarian serous cystadenocarcinoma |
title | Identification of biomarkers complementary to homologous recombination deficiency for improving the clinical outcome of ovarian serous cystadenocarcinoma |
title_full | Identification of biomarkers complementary to homologous recombination deficiency for improving the clinical outcome of ovarian serous cystadenocarcinoma |
title_fullStr | Identification of biomarkers complementary to homologous recombination deficiency for improving the clinical outcome of ovarian serous cystadenocarcinoma |
title_full_unstemmed | Identification of biomarkers complementary to homologous recombination deficiency for improving the clinical outcome of ovarian serous cystadenocarcinoma |
title_short | Identification of biomarkers complementary to homologous recombination deficiency for improving the clinical outcome of ovarian serous cystadenocarcinoma |
title_sort | identification of biomarkers complementary to homologous recombination deficiency for improving the clinical outcome of ovarian serous cystadenocarcinoma |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131501/ https://www.ncbi.nlm.nih.gov/pubmed/34047476 http://dx.doi.org/10.1002/ctm2.399 |
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