The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer
文献类型：期刊论文
| 作者 | Widschwendter, Martin2; Evans, Iona2; Jones, Allison2; Ghazali, Shohreh2; Reisel, Daniel2; Teschendorff, Andrew E.2,6; Ryan, Andy2; Menon, Usha2; Zikan, Michal1,3; Cibula, David1,3 |
| 刊名 | GENOME MEDICINE
 |
| 出版日期 | 2017 |
| 卷号 | 9期号:-页码:116 |
| 关键词 | Cell-free DNA DNA methylation Serum DNA Ovarian cancer Early diagnosis Screening Personalized treatment |
| ISSN号 | 1756-994X |
| DOI | 10.1186/s13073-017-0500-7 |
| 文献子类 | Article |
| 英文摘要 | Background: Despite a myriad of attempts in the last three decades to diagnose ovarian cancer (OC) earlier, this clinical aim still remains a significant challenge. Aberrant methylation patterns of linked CpGs analyzed in DNA fragments shed by cancers into the bloodstream (i.e. cell-free DNA) can provide highly specific signals indicating cancer presence. Methods: We analyzed 699 cancerous and non-cancerous tissues using a methylation array or reduced representation bisulfite sequencing to discover the most specific OC methylation patterns. A three-DNA-methylation-serum-marker panel was developed using targeted ultra-high coverage bisulfite sequencing in 151 women and validated in 250 women with various conditions, particularly in those associated with high CA125 levels (endometriosis and other benign pelvic masses), serial samples from 25 patients undergoing neoadjuvant chemotherapy, and a nested case control study of 172 UKCTOCS control arm participants which included serum samples up to two years before OC diagnosis. Results: The cell-free DNA amount and average fragment size in the serum samples was up to ten times higher than average published values (based on samples that were immediately processed) due to leakage of DNA from white blood cells owing to delayed time to serum separation. Despite this, the marker panel discriminated high grade serous OC patients from healthy women or patients with a benign pelvic mass with specificity/sensitivity of 90.7% (95% confidence interval [CI] = 84.3-94.8%) and 41.4% (95% CI = 24.1-60.9%), respectively. Levels of all three markers plummeted after exposure to chemotherapy and correctly identified 78% and 86% responders and non-responders (Fisher's exact test, p = 0.04), respectively, which was superior to a CA125 cut-off of 35 IU/mL (20% and 75%). 57.9% (95% CI 34.0-78.9%) of women who developed OC within two years of sample collection were identified with a specificity of 88.1% (95% CI = 77.3-94.3%). Sensitivity and specificity improved further when specifically analyzing CA125 negative samples only (63.6% and 87.5%, respectively). Conclusions: Our data suggest that DNA methylation patterns in cell-free DNA have the potential to detect a proportion of OCs up to two years in advance of diagnosis and may potentially guide personalized treatment. The prospective use of novel collection vials, which stabilize blood cells and reduce background DNA contamination in serum/plasma samples, will facilitate clinical implementation of liquid biopsy analyses. |
| 学科主题 | Genetics & Heredity |
| WOS关键词 | RANDOMIZED CONTROLLED-TRIAL ; METASTATIC BREAST-CANCER ; CELL-FREE DNA ; NEOADJUVANT CHEMOTHERAPY ; PLASMA DNA ; BIOMARKER PERFORMANCE ; COLLABORATIVE TRIAL ; SEPT9 DNA ; MARKER ; CA125 |
| 语种 | 英语 |
| WOS记录号 | WOS:000418664700002 |
| 出版者 | BIOMED CENTRAL LTD |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1120]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic; 2.UCL, Dept Womens Canc, UCL Elizabeth Garrett Anderson Inst Womens Hlth, Med Sch Bldg,Room 340,74 Huntley St, London WC1E 6AU, England; 3.Charles Univ Prague, Gynaecol Oncol Ctr, Dept Obstet & Gynaecol, Fac Med 1, Prague, Czech Republic; 4.GATC Biotech AG, Jakob Stadler Pl 7, D-78467 Constance, Germany; 5.Genedata AG, Margarethenstr 38, CH-4053 Basel, Switzerland; 6.Shanghai Inst Biol Sci, CAS Max Planck Partner Inst Computat Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Widschwendter, Martin,Evans, Iona,Jones, Allison,et al. The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer[J]. GENOME MEDICINE,2017,9(-):116. |
| APA | Widschwendter, Martin.,Evans, Iona.,Jones, Allison.,Ghazali, Shohreh.,Reisel, Daniel.,...&,.(2017).The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer.GENOME MEDICINE,9(-),116. |
| MLA | Widschwendter, Martin,et al."The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer".GENOME MEDICINE 9.-(2017):116. |
入库方式： OAI收割
来源：上海营养与健康研究所
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