Abstract
BackgroundSerum 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.MethodscfDNA 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.ResultsMedian 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).ConclusionsSerum 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.
Highlights
Serum cell-free DNA holds promise as a non-invasive cancer biomarker
Gressel et al J Transl Med (2020) 18:323 relative to detection at later stages of disease, especially for high-risk, high-grade histologies such as uterine papillary serous carcinoma (UPSC), clear cell carcinoma (CCC), carcinosarcoma (CS) and leiomyosarcoma (LMS) which represent less than 10% of uterine cancers, but are responsible for as many as 20–39% of uterine cancer-related deaths [2, 3]
A broad range of uterine histologies was represented including all grades of endometrioid adenocarcinoma (EAC, N = 47), uterine papillary serous carcinoma (UPSC, N = 15), Table 1 Clinical and pathologic data of patients included in the study stratified by uterine cancer histologic subtype
Summary
Serum cell-free DNA (cfDNA) holds promise as a non-invasive cancer biomarker. Detection of uterine cancer is associated with improved survival. Gressel et al J Transl Med (2020) 18:323 relative to detection at later stages of disease, especially for high-risk, high-grade histologies such as uterine papillary serous carcinoma (UPSC), clear cell carcinoma (CCC), carcinosarcoma (CS) and leiomyosarcoma (LMS) which represent less than 10% of uterine cancers, but are responsible for as many as 20–39% of uterine cancer-related deaths [2, 3]. Diagnosis is traditionally made using an endometrial biopsy which is a painful and invasive procedure associated with potential bleeding, infection and uterine perforation. There exists an unmet need for a non-invasive serum test for early uterine cancer diagnosis and longitudinal follow-up, especially to aid in the identification of high-risk uterine cancer, which behaves aggressively and has a propensity to metastasize
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