Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer
Extracellular vesicles (EV) and their tumor-supporting cargos provide a promising translational potential in liquid biopsies for risk assessment of epithelial ovarian cancer (EOC) patients frequently relapsing, despite initial complete therapy responses. As the immune checkpoint molecule HLA-G, whic...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/8/1106 |
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| author | Esther Schwich Vera Rebmann Peter A. Horn Alexander A. Celik Christina Bade-Döding Rainer Kimmig Sabine Kasimir-Bauer Paul Buderath |
| author_facet | Esther Schwich Vera Rebmann Peter A. Horn Alexander A. Celik Christina Bade-Döding Rainer Kimmig Sabine Kasimir-Bauer Paul Buderath |
| author_sort | Esther Schwich |
| collection | DOAJ |
| description | Extracellular vesicles (EV) and their tumor-supporting cargos provide a promising translational potential in liquid biopsies for risk assessment of epithelial ovarian cancer (EOC) patients frequently relapsing, despite initial complete therapy responses. As the immune checkpoint molecule HLA-G, which is operative in immune-escape, can be released by EV, we evaluate the abundance of EV and its vesicular-bound amount of HLA-G (HLA-G<sub>EV</sub>) as a biomarker in EOC. After enrichment of EV from plasma samples, we determined the EV particle number and amount of HLA-G<sub>EV</sub> by nanoparticle tracking analysis or ELISA. The association of results with the clinical status/outcome revealed that both, EV particle number and HLA-G<sub>EV</sub> were significantly elevated in EOC patients, compared to healthy females. However, elevated levels of HLA-G<sub>EV</sub>, but not EV numbers, were exclusively associated with a disadvantageous clinical status/outcome, including residual tumor, presence of circulating tumor cells, and disease progression. High HLA-G<sub>EV</sub> status was an independent predictor of progression, besides residual tumor burden and platinum-sensitivity. Especially among patients without residual tumor burden or with platinum-sensitivity, HLA-G<sub>EV</sub> identified patients with high risk of progression. Thus, this study highlights HLA-G<sub>EV</sub> as a potential novel biomarker for risk assessment of EOC patients with a rather beneficial prognosis defined by platinum-sensitivity or lack of residual tumor burden. |
| first_indexed | 2024-03-12T19:20:20Z |
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| id | doaj.art-d8a4df8bb3754d39817d1201f0bd05f1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:20:20Z |
| publishDate | 2019-08-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d8a4df8bb3754d39817d1201f0bd05f12023-08-02T05:15:11ZengMDPI AGCancers2072-66942019-08-01118110610.3390/cancers11081106cancers11081106Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian CancerEsther Schwich0Vera Rebmann1Peter A. Horn2Alexander A. Celik3Christina Bade-Döding4Rainer Kimmig5Sabine Kasimir-Bauer6Paul Buderath7Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstr. 179, 45147 Essen, GermanyInstitute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstr. 179, 45147 Essen, GermanyInstitute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Virchowstr. 179, 45147 Essen, GermanyInstitute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyInstitute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyDepartment for Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, GermanyDepartment for Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, GermanyDepartment for Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, GermanyExtracellular vesicles (EV) and their tumor-supporting cargos provide a promising translational potential in liquid biopsies for risk assessment of epithelial ovarian cancer (EOC) patients frequently relapsing, despite initial complete therapy responses. As the immune checkpoint molecule HLA-G, which is operative in immune-escape, can be released by EV, we evaluate the abundance of EV and its vesicular-bound amount of HLA-G (HLA-G<sub>EV</sub>) as a biomarker in EOC. After enrichment of EV from plasma samples, we determined the EV particle number and amount of HLA-G<sub>EV</sub> by nanoparticle tracking analysis or ELISA. The association of results with the clinical status/outcome revealed that both, EV particle number and HLA-G<sub>EV</sub> were significantly elevated in EOC patients, compared to healthy females. However, elevated levels of HLA-G<sub>EV</sub>, but not EV numbers, were exclusively associated with a disadvantageous clinical status/outcome, including residual tumor, presence of circulating tumor cells, and disease progression. High HLA-G<sub>EV</sub> status was an independent predictor of progression, besides residual tumor burden and platinum-sensitivity. Especially among patients without residual tumor burden or with platinum-sensitivity, HLA-G<sub>EV</sub> identified patients with high risk of progression. Thus, this study highlights HLA-G<sub>EV</sub> as a potential novel biomarker for risk assessment of EOC patients with a rather beneficial prognosis defined by platinum-sensitivity or lack of residual tumor burden.https://www.mdpi.com/2072-6694/11/8/1106extracellular vesiclesvesicular-bound HLA-GHLA-G<sub>EV</sub>epithelial ovarian cancer (EOC)liquid biopsyplatinum therapyresidual tumor burdencirculating tumor cells |
| spellingShingle | Esther Schwich Vera Rebmann Peter A. Horn Alexander A. Celik Christina Bade-Döding Rainer Kimmig Sabine Kasimir-Bauer Paul Buderath Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer Cancers extracellular vesicles vesicular-bound HLA-G HLA-G<sub>EV</sub> epithelial ovarian cancer (EOC) liquid biopsy platinum therapy residual tumor burden circulating tumor cells |
| title | Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer |
| title_full | Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer |
| title_fullStr | Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer |
| title_full_unstemmed | Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer |
| title_short | Vesicular-Bound HLA-G as a Predictive Marker for Disease Progression in Epithelial Ovarian Cancer |
| title_sort | vesicular bound hla g as a predictive marker for disease progression in epithelial ovarian cancer |
| topic | extracellular vesicles vesicular-bound HLA-G HLA-G<sub>EV</sub> epithelial ovarian cancer (EOC) liquid biopsy platinum therapy residual tumor burden circulating tumor cells |
| url | https://www.mdpi.com/2072-6694/11/8/1106 |
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