各种细胞外 DNA 亚型在卵巢癌患者中的预后价值。
Prognostic value of various subtypes of extracellular DNA in ovarian cancer patients.
机构信息
2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Klenova 1, 833 10, Bratislava, Slovak Republic.
Translational Research Unit, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
出版信息
J Ovarian Res. 2018 Sep 22;11(1):85. doi: 10.1186/s13048-018-0459-z.
BACKGROUND
Patients with ovarian cancer represent a heterogeneous population with a variable prognosis and response to chemotherapy. Plasma DNA has been shown to have a prognostic value in different types of cancer including ovarian carcinoma. Whether total circulating DNA, which can be assessed much easier without knowing the tumor-specific mutations, has similar informative value is currently unknown. The aim of this study was to evaluate the prognostic value of extracellular DNA in advanced ovarian cancer.
METHODS
This prospective study included 67 patients (pts) with ovarian cancer treated with 1st line paclitaxel and carboplatin (25 pts) and paclitaxel, carboplatin and bevacizumab (42 pts). Thirty-five patients had optimal surgical debulking before chemotherapy. Extracellular DNA was quantified using real time PCR before administration of chemotherapy (67 pts) and after 6 cycles of chemotherapy (44 pts).
RESULTS
Total extracellular DNA (ecDNA), as well as extracellular DNA of nuclear (nDNA) and mitochondrial origin (mtDNA) significantly (p < 0.05) decreased after 6 cycles of chemotherapy (by 54%, 63% and 52%, respectively. Patients with stage I disease had significantly lower mtDNA compared to patients with stage II-IV (8604 vs. 16, 984 ge/mL, p = 0.03). Patients with lower baseline nDNA had superior progression-free (HR = 0.35 (0.14-0.86)) and overall survival (HR = 0.18 (0.04-0.77). The prognostic value of nDNA was confirmed independent of tumor stage and confirmed in multivariate analysis.
CONCLUSIONS
Our data suggest that ecDNA of both, nuclear and mitochondrial origin could be added to prognostic markers in ovarian cancer. Analysis of ecDNA does not require the knowledge of tumor-specific mutations in contrast to the quantification of tumor-derived ecDNA. Study of the dynamics and cell type-specific source of the ecDNA could shed light on its biology in cancer and might help to direct the treatment of ovarian cancer.
背景
卵巢癌患者是一个异质性群体，其预后和对化疗的反应各不相同。已有研究表明，血浆 DNA 在包括卵巢癌在内的不同类型癌症中具有预后价值。目前尚不清楚是否总循环 DNA（无需了解肿瘤特异性突变即可更轻松地评估）具有相似的信息价值。本研究旨在评估晚期卵巢癌中外周血游离 DNA 的预后价值。
方法
本前瞻性研究纳入了接受一线紫杉醇加卡铂治疗的 67 例卵巢癌患者（25 例）和紫杉醇、卡铂和贝伐珠单抗治疗的 42 例卵巢癌患者。35 例患者在化疗前进行了最佳的肿瘤细胞减灭术。化疗前（67 例）和化疗 6 个周期后（44 例），采用实时 PCR 定量检测细胞外 DNA。
结果
总细胞外 DNA（ecDNA）以及核（nDNA）和线粒体起源的细胞外 DNA（mtDNA）在化疗 6 个周期后显著降低（分别下降 54%、63%和 52%，p<0.05）。I 期疾病患者的 mtDNA 明显低于 II-IV 期患者（8604 与 16、984 ge/mL，p=0.03）。基线 nDNA 水平较低的患者无进展生存期（HR=0.35（0.14-0.86））和总生存期（HR=0.18（0.04-0.77））更长。nDNA 的预后价值独立于肿瘤分期，并在多变量分析中得到证实。
结论
我们的数据表明，核和线粒体来源的 ecDNA 可能会被添加到卵巢癌的预后标志物中。与定量肿瘤衍生的 ecDNA 相比，分析 ecDNA 不需要了解肿瘤特异性突变。对 ecDNA 的动态变化及其细胞类型特异性来源的研究可以揭示其在癌症中的生物学特性，并可能有助于指导卵巢癌的治疗。
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