Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study
Abstract Introduction Low serum selenium and altered tumour RNA expression of certain selenoproteins are associated with a poor breast cancer prognosis. Selenoprotein expression stringently depends on selenium availability, hence circulating selenium may interact with tumour selenoprotein expression...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-023-04502-y |
| _version_ | 1827708701651238912 |
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| author | Kamil Demircan Ylva Bengtsson Thilo Samson Chillon Johan Vallon-Christersson Qian Sun Christer Larsson Martin Malmberg Lao H. Saal Lisa Rydén Åke Borg Jonas Manjer Lutz Schomburg |
| author_facet | Kamil Demircan Ylva Bengtsson Thilo Samson Chillon Johan Vallon-Christersson Qian Sun Christer Larsson Martin Malmberg Lao H. Saal Lisa Rydén Åke Borg Jonas Manjer Lutz Schomburg |
| author_sort | Kamil Demircan |
| collection | DOAJ |
| description | Abstract Introduction Low serum selenium and altered tumour RNA expression of certain selenoproteins are associated with a poor breast cancer prognosis. Selenoprotein expression stringently depends on selenium availability, hence circulating selenium may interact with tumour selenoprotein expression. However, there is no matched analysis to date. Methods This study included 1453 patients with newly diagnosed breast cancer from the multicentric prospective Sweden Cancerome Analysis Network – Breast study. Total serum selenium, selenoprotein P and glutathione peroxidase 3 were analysed at time of diagnosis. Bulk RNA-sequencing was conducted in matched tumour tissues. Fully adjusted Cox regression models with an interaction term were employed to detect dose-dependent interactions of circulating selenium with the associations of tumour selenoprotein mRNA expression and mortality. Results 237 deaths were recorded within ~ 9 years follow-up. All three serum selenium biomarkers correlated positively (p < 0.001). All selenoproteins except for GPX6 were expressed in tumour tissues. Single cell RNA-sequencing revealed a heterogeneous expression pattern in the tumour microenvironment. Circulating selenium correlated positively with tumour SELENOW and SELENON expression (p < 0.001). In fully adjusted models, the associations of DIO1, DIO3 and SELENOM with mortality were dose-dependently modified by serum selenium (p < 0.001, p = 0.020, p = 0.038, respectively). With increasing selenium, DIO1 and SELENOM associated with lower, whereas DIO3 expression associated with higher mortality. Association of DIO1 with lower mortality was only apparent in patients with high selenium [above median (70.36 µg/L)], and the HR (95%CI) for one-unit increase in log(FPKM + 1) was 0.70 (0.50–0.98). Conclusions This first unbiased analysis of serum selenium with the breast cancer selenotranscriptome identified an effect-modification of selenium on the associations of DIO1, SELENOM, and DIO3 with prognosis. Selenium substitution in patients with DIO1-expressing tumours merits consideration to improve survival. |
| first_indexed | 2024-03-10T17:08:16Z |
| format | Article |
| id | doaj.art-cff4db4e410142088f7f14e1fff6b03b |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-10T17:08:16Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-cff4db4e410142088f7f14e1fff6b03b2023-11-20T10:44:59ZengBMCJournal of Translational Medicine1479-58762023-09-0121111210.1186/s12967-023-04502-yMatched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective studyKamil Demircan0Ylva Bengtsson1Thilo Samson Chillon2Johan Vallon-Christersson3Qian Sun4Christer Larsson5Martin Malmberg6Lao H. Saal7Lisa Rydén8Åke Borg9Jonas Manjer10Lutz Schomburg11Institute for Experimental Endocrinology, Cardiovascular-Metabolic-Renal (CMR)-Research Center, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthDepartment of Surgery, Skåne University Hospital Malmö, Lund UniversityInstitute for Experimental Endocrinology, Cardiovascular-Metabolic-Renal (CMR)-Research Center, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthDivision of Oncology, Department of Clinical Sciences Lund, Lund UniversityInstitute for Experimental Endocrinology, Cardiovascular-Metabolic-Renal (CMR)-Research Center, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthDivision of Translational Cancer Research, Department of Laboratory Medicine, Lund UniversityDepartment of Oncology, Skåne University HospitalDivision of Oncology, Department of Clinical Sciences Lund, Lund UniversityDepartment of Surgery, Skåne University Hospital Malmö, Lund UniversityDivision of Oncology, Department of Clinical Sciences Lund, Lund UniversityDepartment of Surgery, Skåne University Hospital Malmö, Lund UniversityInstitute for Experimental Endocrinology, Cardiovascular-Metabolic-Renal (CMR)-Research Center, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthAbstract Introduction Low serum selenium and altered tumour RNA expression of certain selenoproteins are associated with a poor breast cancer prognosis. Selenoprotein expression stringently depends on selenium availability, hence circulating selenium may interact with tumour selenoprotein expression. However, there is no matched analysis to date. Methods This study included 1453 patients with newly diagnosed breast cancer from the multicentric prospective Sweden Cancerome Analysis Network – Breast study. Total serum selenium, selenoprotein P and glutathione peroxidase 3 were analysed at time of diagnosis. Bulk RNA-sequencing was conducted in matched tumour tissues. Fully adjusted Cox regression models with an interaction term were employed to detect dose-dependent interactions of circulating selenium with the associations of tumour selenoprotein mRNA expression and mortality. Results 237 deaths were recorded within ~ 9 years follow-up. All three serum selenium biomarkers correlated positively (p < 0.001). All selenoproteins except for GPX6 were expressed in tumour tissues. Single cell RNA-sequencing revealed a heterogeneous expression pattern in the tumour microenvironment. Circulating selenium correlated positively with tumour SELENOW and SELENON expression (p < 0.001). In fully adjusted models, the associations of DIO1, DIO3 and SELENOM with mortality were dose-dependently modified by serum selenium (p < 0.001, p = 0.020, p = 0.038, respectively). With increasing selenium, DIO1 and SELENOM associated with lower, whereas DIO3 expression associated with higher mortality. Association of DIO1 with lower mortality was only apparent in patients with high selenium [above median (70.36 µg/L)], and the HR (95%CI) for one-unit increase in log(FPKM + 1) was 0.70 (0.50–0.98). Conclusions This first unbiased analysis of serum selenium with the breast cancer selenotranscriptome identified an effect-modification of selenium on the associations of DIO1, SELENOM, and DIO3 with prognosis. Selenium substitution in patients with DIO1-expressing tumours merits consideration to improve survival.https://doi.org/10.1186/s12967-023-04502-ySelenoproteinsSELENOPGlutathione peroxidaseThyroid hormonesPrognosis |
| spellingShingle | Kamil Demircan Ylva Bengtsson Thilo Samson Chillon Johan Vallon-Christersson Qian Sun Christer Larsson Martin Malmberg Lao H. Saal Lisa Rydén Åke Borg Jonas Manjer Lutz Schomburg Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study Journal of Translational Medicine Selenoproteins SELENOP Glutathione peroxidase Thyroid hormones Prognosis |
| title | Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study |
| title_full | Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study |
| title_fullStr | Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study |
| title_full_unstemmed | Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study |
| title_short | Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study |
| title_sort | matched analysis of circulating selenium with the breast cancer selenotranscriptome a multicentre prospective study |
| topic | Selenoproteins SELENOP Glutathione peroxidase Thyroid hormones Prognosis |
| url | https://doi.org/10.1186/s12967-023-04502-y |
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