上皮性卵巢癌的循环染色体外环状DNA反映化疗反应和复发。

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Jing Wang , Zhicheng Xu , Yan Zhong , Jiaxuan Yang , Zongle Yang , Wei Ye , Qiang Wu , Youwen Du , Jianghao Xing , Mafei Xu
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引用次数: 0

摘要

血浆中无细胞的染色体外环状DNA (eccDNA)为监测上皮性卵巢癌(EOC)的进展提供了一个优势。我们从30例EOC患者治疗前(T0时间点)和4例健康人的血浆样本中分离出eccDNA。我们对16例EOC患者进行随访,收集第3、4个化疗疗程(T1)和最后一个化疗疗程后6个月(F)的配对eccDNA样本。将患者分为完全缓解组(CR)、部分缓解组(PR)和复发组(RC)三组。我们比较了各组间标准化的每百万映射读数(EPM),并评估了每条染色体上eccDNA的分布。然后,对每条染色体前5%覆盖区域内的eccDNA进行注释,并对顶端基因进行预后分析。我们发现EOC患者的eccDNA水平明显更高,编码外显子区域的覆盖率更高。值得注意的是,在治疗期间,CR组的循环eccDNA普遍增加,而PR和RC组的循环eccDNA则有所下降。我们的结果显示,T1和T0之间epm的倍数变化将PR和RC患者与CR患者区分开来,曲线下面积(AUC)为0.71。此外,我们发现SCARB1和PDE10A两个基因,其epm能够预测EOC患者的预后,auc分别为0.86和0.83。因此,我们的研究为基于循环eccDNA趋势预测EOC患者化疗敏感性的新方法提供了有价值的初步见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating extrachromosomal circular DNA in epithelial ovarian cancer reflects chemotherapeutic response and recurrence
Cell-free extrachromosomal circular DNA (eccDNA) in the plasma provides an advantage for monitoring epithelial ovarian cancer (EOC) progression. We isolated eccDNA from plasma samples of 30 EOC patients before treatment (T0 time point) and 4 healthy individuals. We followed 16 EOC patients, collecting paired eccDNA samples between the 3rd and 4th course of chemotherapy (T1) and 6 months after the last course of chemotherapy (F). The patients were divided into three groups, including complete remission (CR) group, partial remission group (PR), and relapse group (RC). We compared the normalized eccDNA count per million mapped reads (EPM) among all the groups and assessed the distribution of eccDNA on each chromosome. Then, the eccDNA within the top 5 % coverage regions of each chromosome were annotated, and the top genes were analyzed for prognosis. We found that EOC patients exhibited significantly higher levels of eccDNA, with higher coverage in coding exon regions. Notably, circulating eccDNA was generally increased in the CR group, while decreased in the PR and RC group during treatment. Our results showed that the fold change of EPMs between the T1 and T0 distinguished PR and RC patients from CR patients, with area under the curve (AUC) of 0.71. Additionally, we identified two genes, SCARB1 and PDE10A, whose EPMs were able to predict prognosis in EOC patients, with AUCs of 0.86 and 0.83, respectively. Thus, our study offers valuable preliminary insights into a novel approach for predicting chemotherapy sensitivity in EOC patients, based on the trends of circulating eccDNA.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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