Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast Cancer
There is a great need for non-invasive tools that inform of an early molecular response to cancer therapeutic treatment. Here, we tested the hypothesis that proteolytically resistant proteins could be candidate circulating tumor biomarkers for cancer therapy. Proteins resistant to proteolysis are dr...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/16/3858 |
| _version_ | 1797446624937508864 |
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| author | Mercè Juliachs Mireia Pujals Chiara Bellio Nathalie Meo-Evoli Juan M. Duran Esther Zamora Mireia Parés Anna Suñol Olga Méndez Alex Sánchez-Pla Francesc Canals Cristina Saura Josep Villanueva |
| author_facet | Mercè Juliachs Mireia Pujals Chiara Bellio Nathalie Meo-Evoli Juan M. Duran Esther Zamora Mireia Parés Anna Suñol Olga Méndez Alex Sánchez-Pla Francesc Canals Cristina Saura Josep Villanueva |
| author_sort | Mercè Juliachs |
| collection | DOAJ |
| description | There is a great need for non-invasive tools that inform of an early molecular response to cancer therapeutic treatment. Here, we tested the hypothesis that proteolytically resistant proteins could be candidate circulating tumor biomarkers for cancer therapy. Proteins resistant to proteolysis are drastically under-sampled by current proteomic workflows. These proteins could be reliable sensors for the response to therapy since they are likely to stay longer in circulation. We selected manganese superoxide dismutase (SOD2), a mitochondrial redox enzyme, from a screening of proteolytic resistant proteins in breast cancer (BC). First, we confirmed the robustness of SOD2 and determined that its proteolytic resistance is mediated by its quaternary protein structure. We also proved that the release of SOD2 upon chemotherapy treatment correlates with cell death in BC cells. Then, after confirming that SOD2 is very stable in human serum, we sought to measure its circulating levels in a cohort of BC patients undergoing neoadjuvant therapy. The results showed that circulating levels of SOD2 increased when patients responded to the treatment according to the tumor shrinkage during neoadjuvant chemotherapy. Therefore, the measurement of SOD2 levels in plasma could improve the non-invasive monitoring of the therapeutic treatment in breast cancer patients. The identification of circulating biomarkers linked to the tumor cell death induced by treatment could be useful for monitoring the action of the large number of cancer drugs currently used in clinics. We envision that our approach could help uncover candidate tumor biomarkers to measure a tumor’s response to cancer therapy in real time by sampling the tumor throughout the course of treatment. |
| first_indexed | 2024-03-09T13:43:17Z |
| format | Article |
| id | doaj.art-71b081b94f5c46398fbe60635f32029b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:43:17Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-71b081b94f5c46398fbe60635f32029b2023-11-30T21:03:31ZengMDPI AGCancers2072-66942022-08-011416385810.3390/cancers14163858Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast CancerMercè Juliachs0Mireia Pujals1Chiara Bellio2Nathalie Meo-Evoli3Juan M. Duran4Esther Zamora5Mireia Parés6Anna Suñol7Olga Méndez8Alex Sánchez-Pla9Francesc Canals10Cristina Saura11Josep Villanueva12Vall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainVall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainVall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainVall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainVall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainDepartment of Medical Oncology, Vall d’Hebron University Hospital, 08035 Barcelona, SpainVall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainVall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainVall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainGenetics Microbiology and Statistics Department, Universitat de Barcelona, 08028 Barcelona, SpainVall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainDepartment of Medical Oncology, Vall d’Hebron University Hospital, 08035 Barcelona, SpainVall d’Hebron Institut of Oncology (VHIO), 08035 Barcelona, SpainThere is a great need for non-invasive tools that inform of an early molecular response to cancer therapeutic treatment. Here, we tested the hypothesis that proteolytically resistant proteins could be candidate circulating tumor biomarkers for cancer therapy. Proteins resistant to proteolysis are drastically under-sampled by current proteomic workflows. These proteins could be reliable sensors for the response to therapy since they are likely to stay longer in circulation. We selected manganese superoxide dismutase (SOD2), a mitochondrial redox enzyme, from a screening of proteolytic resistant proteins in breast cancer (BC). First, we confirmed the robustness of SOD2 and determined that its proteolytic resistance is mediated by its quaternary protein structure. We also proved that the release of SOD2 upon chemotherapy treatment correlates with cell death in BC cells. Then, after confirming that SOD2 is very stable in human serum, we sought to measure its circulating levels in a cohort of BC patients undergoing neoadjuvant therapy. The results showed that circulating levels of SOD2 increased when patients responded to the treatment according to the tumor shrinkage during neoadjuvant chemotherapy. Therefore, the measurement of SOD2 levels in plasma could improve the non-invasive monitoring of the therapeutic treatment in breast cancer patients. The identification of circulating biomarkers linked to the tumor cell death induced by treatment could be useful for monitoring the action of the large number of cancer drugs currently used in clinics. We envision that our approach could help uncover candidate tumor biomarkers to measure a tumor’s response to cancer therapy in real time by sampling the tumor throughout the course of treatment.https://www.mdpi.com/2072-6694/14/16/3858manganese superoxide dismutase (SOD2)response biomarkersbreast cancersecretome |
| spellingShingle | Mercè Juliachs Mireia Pujals Chiara Bellio Nathalie Meo-Evoli Juan M. Duran Esther Zamora Mireia Parés Anna Suñol Olga Méndez Alex Sánchez-Pla Francesc Canals Cristina Saura Josep Villanueva Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast Cancer Cancers manganese superoxide dismutase (SOD2) response biomarkers breast cancer secretome |
| title | Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast Cancer |
| title_full | Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast Cancer |
| title_fullStr | Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast Cancer |
| title_full_unstemmed | Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast Cancer |
| title_short | Circulating SOD2 Is a Candidate Response Biomarker for Neoadjuvant Therapy in Breast Cancer |
| title_sort | circulating sod2 is a candidate response biomarker for neoadjuvant therapy in breast cancer |
| topic | manganese superoxide dismutase (SOD2) response biomarkers breast cancer secretome |
| url | https://www.mdpi.com/2072-6694/14/16/3858 |
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