Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, Korea.
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Cancer Res Treat. 2020 Jul;52(3):779-788. doi: 10.4143/crt.2019.700. Epub 2020 Feb 28.
The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients.
Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients.
Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53 was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC.
Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.
本研究旨在确定来源于上皮性卵巢癌(EOC)患者腹水和连续血浆样本的循环肿瘤 DNA(ctDNA)的临床应用价值。
我们采用靶向二代测序技术,分析了总共 55 例 EOC 样本,包括腹水和连续血浆中的 ctDNA 以及肿瘤组织中的 gDNA。肿瘤组织和腹水在肿瘤减灭术期间采集,血浆样本在手术前后采集。由于 1 例 EOC 患者接受了二次肿瘤减灭术,因此从 10 例患者中总共获得了 11 个肿瘤组织、33 个血浆样本和 11 个腹水样本。
在 10 例患者中,有 9 例(90%)患者的肿瘤组织和腹水 ctDNA 中均存在体细胞突变。这种突变一致性通过相关性分析得到了证实。在复发性/进展性卵巢癌中,腹水和肿瘤组织之间的突变一致性是有效的。TP53 是最常检测到突变的基因。连续的血浆样本中的 ctDNA 可以在与癌症抗原 125(CA125)相似或更快的时间点识别出 EOC 的进展/复发,CA125 是一种已确立的用于 EOC 的血清蛋白肿瘤标志物。
我们的数据表明,腹水 ctDNA 可用于鉴定卵巢癌的突变图谱,以制定治疗策略。