Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer
Abstract Background Serum cell-free DNA (cfDNA) holds promise as a non-invasive cancer biomarker. The objective of this study was to evaluate the association of cfDNA concentration with clinicopathologic variables of poor prognosis and overall survival among women with uterine cancer compared to ben...
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12967-020-02493-8 |
| _version_ | 1828901337809551360 |
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| author | Gregory M. Gressel Elaine C. Maggi Bryan E. Harmon Kenny Q. Ye D. Y. S. Kuo Siobhan M. Dolan Cristina Montagna |
| author_facet | Gregory M. Gressel Elaine C. Maggi Bryan E. Harmon Kenny Q. Ye D. Y. S. Kuo Siobhan M. Dolan Cristina Montagna |
| author_sort | Gregory M. Gressel |
| collection | DOAJ |
| description | Abstract Background Serum cell-free DNA (cfDNA) holds promise as a non-invasive cancer biomarker. The objective of this study was to evaluate the association of cfDNA concentration with clinicopathologic variables of poor prognosis and overall survival among women with uterine cancer compared to benign cancer-free controls. Methods cfDNA was extracted from the serum of 91 women with multiple uterine cancer histologies and 22 post-menopausal controls without cancer. Low molecular weight (LMW) cfDNA was separated from contaminating genomic high molecular weight cfDNA using paramagnetic bead purification and its concentration was measured using fluorometric quantification. Clinicopathologic data was abstracted from the electronic medical record. The association between serum cfDNA concentration, clinicopathologic variables, and overall survival was assessed using linear regression modelling, Cox proportional hazards modelling, and the Kaplan–Meier method. Results Median total serum cfDNA concentration for the cohort was 69.2 ng/mL (IQR 37.4, 132.3) and median LMW cfDNA concentration was 23.8 ng/mL (IQR 14.9, 44.4). There were no significant differences in total serum cfDNA concentration with any clinicopathologic variables. However, LMW cfDNA concentration was significantly higher in serum of women with cancer (25.8 ng/mL IQR 16.0, 49.6) compared to benign controls (15.5 ng/mL IQR 9.3, 25.8 ng/mL) (p < 0.01). It is also significantly higher among women with early stage cancer than benign controls (p < 0.01). There were also significant associations between LMW cfDNA concentration and stage of cancer (p = 0.01) and histology (p = 0.02). Patients with leiomyosarcoma and carcinosarcoma had higher cfDNA concentrations than those with endometrioid cancer. Over a median follow-up of 51.9 months, 75th percentile for overall survival for women with cancer was 24.0 months. Higher LMW cfDNA concentrations is associated with lower survival among women with cancer (p < 0.01). Conclusions Serum LMW cfDNA concentration is associated with overall survival in women with uterine cancer, and it is higher among women with uterine cancer compared to those of controls. |
| first_indexed | 2024-12-13T15:59:47Z |
| format | Article |
| id | doaj.art-ad820cf7bb054e1b87d07420fe9597f6 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-13T15:59:47Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj.art-ad820cf7bb054e1b87d07420fe9597f62022-12-21T23:39:13ZengBMCJournal of Translational Medicine1479-58762020-08-011811910.1186/s12967-020-02493-8Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancerGregory M. Gressel0Elaine C. Maggi1Bryan E. Harmon2Kenny Q. Ye3D. Y. S. Kuo4Siobhan M. Dolan5Cristina Montagna6Department of Obstetrics & Gynecology and Women’s Health, Albert Einstein College of MedicineDepartment of Genetics, Albert Einstein College of Medicine Price Center/Block Research PavilionDepartment of Pathology, Albert Einstein College of MedicineDepartment of Epidemiology & Population Health, Albert Einstein College of MedicineDepartment of Obstetrics & Gynecology and Women’s Health, Albert Einstein College of MedicineDepartment of Obstetrics & Gynecology and Women’s Health, Albert Einstein College of MedicineDepartment of Genetics, Albert Einstein College of Medicine Price Center/Block Research PavilionAbstract Background Serum cell-free DNA (cfDNA) holds promise as a non-invasive cancer biomarker. The objective of this study was to evaluate the association of cfDNA concentration with clinicopathologic variables of poor prognosis and overall survival among women with uterine cancer compared to benign cancer-free controls. Methods cfDNA was extracted from the serum of 91 women with multiple uterine cancer histologies and 22 post-menopausal controls without cancer. Low molecular weight (LMW) cfDNA was separated from contaminating genomic high molecular weight cfDNA using paramagnetic bead purification and its concentration was measured using fluorometric quantification. Clinicopathologic data was abstracted from the electronic medical record. The association between serum cfDNA concentration, clinicopathologic variables, and overall survival was assessed using linear regression modelling, Cox proportional hazards modelling, and the Kaplan–Meier method. Results Median total serum cfDNA concentration for the cohort was 69.2 ng/mL (IQR 37.4, 132.3) and median LMW cfDNA concentration was 23.8 ng/mL (IQR 14.9, 44.4). There were no significant differences in total serum cfDNA concentration with any clinicopathologic variables. However, LMW cfDNA concentration was significantly higher in serum of women with cancer (25.8 ng/mL IQR 16.0, 49.6) compared to benign controls (15.5 ng/mL IQR 9.3, 25.8 ng/mL) (p < 0.01). It is also significantly higher among women with early stage cancer than benign controls (p < 0.01). There were also significant associations between LMW cfDNA concentration and stage of cancer (p = 0.01) and histology (p = 0.02). Patients with leiomyosarcoma and carcinosarcoma had higher cfDNA concentrations than those with endometrioid cancer. Over a median follow-up of 51.9 months, 75th percentile for overall survival for women with cancer was 24.0 months. Higher LMW cfDNA concentrations is associated with lower survival among women with cancer (p < 0.01). Conclusions Serum LMW cfDNA concentration is associated with overall survival in women with uterine cancer, and it is higher among women with uterine cancer compared to those of controls.http://link.springer.com/article/10.1186/s12967-020-02493-8Cell-free DNAEndometrial cancerUterine cancerSerum biomarkersSerum DNA |
| spellingShingle | Gregory M. Gressel Elaine C. Maggi Bryan E. Harmon Kenny Q. Ye D. Y. S. Kuo Siobhan M. Dolan Cristina Montagna Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer Journal of Translational Medicine Cell-free DNA Endometrial cancer Uterine cancer Serum biomarkers Serum DNA |
| title | Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer |
| title_full | Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer |
| title_fullStr | Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer |
| title_full_unstemmed | Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer |
| title_short | Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer |
| title_sort | low molecular weight serum cell free dna concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer |
| topic | Cell-free DNA Endometrial cancer Uterine cancer Serum biomarkers Serum DNA |
| url | http://link.springer.com/article/10.1186/s12967-020-02493-8 |
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