Gressel Gregory M, Maggi Elaine C, Harmon Bryan E, Ye Kenny Q, Kuo D Y S, Dolan Siobhan M, Montagna Cristina
Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Genetics, Albert Einstein College of Medicine Price Center/Block Research Pavilion, Room 401, 1301 Morris Park Avenue, Bronx, NY, 10461, USA.
J Transl Med. 2020 Aug 27;18(1):323. doi: 10.1186/s12967-020-02493-8.
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.
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.
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).
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.
血清游离DNA（cfDNA）有望成为一种非侵入性癌症生物标志物。本研究的目的是评估与无癌良性对照相比，子宫癌女性中cfDNA浓度与预后不良的临床病理变量及总生存期之间的关联。
从91例患有多种子宫癌组织学类型的女性血清以及22例无癌绝经后对照的血清中提取cfDNA。使用顺磁珠纯化法从污染的基因组高分子量cfDNA中分离出低分子量（LMW）cfDNA，并使用荧光定量法测量其浓度。临床病理数据从电子病历中提取。使用线性回归模型、Cox比例风险模型和Kaplan-Meier方法评估血清cfDNA浓度、临床病理变量与总生存期之间的关联。
该队列的血清总cfDNA浓度中位数为69.2 ng/mL（四分位间距37.4，132.3），LMW cfDNA浓度中位数为23.8 ng/mL（四分位间距14.9，44.4）。血清总cfDNA浓度与任何临床病理变量均无显著差异。然而，与良性对照（15.5 ng/mL，四分位间距9.3，25.8 ng/mL）相比，癌症女性血清中的LMW cfDNA浓度显著更高（25.8 ng/mL，四分位间距16.0，49.6）（p < 0.01）。早期癌症女性中的LMW cfDNA浓度也显著高于良性对照（p < 0.01）。LMW cfDNA浓度与癌症分期（p = 0.01）和组织学（p = 0.02）之间也存在显著关联。平滑肌肉瘤和癌肉瘤患者的cfDNA浓度高于子宫内膜样癌患者。在中位随访51.9个月期间，癌症女性总生存期的第75百分位数为24.0个月。较高的LMW cfDNA浓度与癌症女性较低的生存率相关（p < 0.01）。
血清LMW cfDNA浓度与子宫癌女性的总生存期相关，并且与对照相比，子宫癌女性中的浓度更高。
