Liquid biopsy with droplet digital PCR targeted to specific mutations in plasma cell-free tumor DNA can detect ovarian cancer recurrence earlier than CA125.
Liquid biopsy with droplet digital PCR targeted to specific mutations in plasma cell-free tumor DNA can detect ovarian cancer recurrence earlier than CA125.
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DOI：
10.1016/j.gore.2021.100847
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发表时间：
2021-11
影响因子：
1.2
通讯作者：
Yasuda J
中科院分区：
文献类型：
--
作者：
Minato T;Ito S;Li B;Fujimori H;Mochizuki M;Yamaguchi K;Tamai K;Shimada M;Tokunaga H;Shigeta S;Sato I;Shima H;Yamada H;Yaegashi N;Yasuda J
应用微滴数字PCR技术检测卵巢癌患者外周血循环肿瘤源性DNA（ctDNA）。在血浆CA 125升高之前，6例复发OC病例中有5例在ddPCR分析中呈阳性。ctDNA等位基因频率增加与OC复发后肿瘤体积增加相关。卵巢癌（OC）是一种难治性妇科肿瘤，即使在通过根治性切除和新辅助化疗完全根除肿瘤组织后，也会在几年内频繁复发。传统的复发标志物CA 125被广泛用于OC切除后的随访，但CA 125在血液中的半衰期较长，对肿瘤复发缺乏动态反应。液体活检技术的最新发展有望克服OC术后复发早期诊断的困难。我们应用微滴数字PCR（ddPCR）技术在随访期间检测OC患者血浆中循环肿瘤源性DNA。来自连续OC患者的11对肿瘤-正常基因组DNA的外显子组测序鉴定了肿瘤特异性突变，并为每个样品选择ddPCR探针。6/11例患者在随访期间出现明显复发（平均无进展生存期为348.3天），所有6例患者在ddPCR分析中均为阳性。此外，6例中有5例在血浆CA 125升高之前ddPCR变为阳性。循环肿瘤DNA（ctDNA）等位基因频率增加与复发后肿瘤体积增加相关。在通过成像检测OC复发中，ddPCR检测ctDNA信号显著早于增加的CA 125（分别为49天和7天前：p < 0.05）。无复发病例血浆中未检测到ctDNA。我们的研究结果表明，通过ddPCR识别ctDNA作为OC复发的早期检测工具的潜力。
Droplet digital PCR was applied to detect circulating tumor-derived DNA (ctDNA) in ovarian cancer (OC) follow-up. Five out of six recurrent OC cases were positive in ddPCR analyses before increased plasma CA125. Increased allele frequency of the ctDNA is associated with increased tumor volume after OC recurrence. No ctDNA was detected in the plasma of recurrence-free OC cases (maximum, 439 PFS days) Ovarian cancer (OC) is an intractable gynecological tumor, and frequent recurrence is experienced within a few years even after the complete eradication of tumor tissues by radical resection and neo-adjuvant chemotherapies. The conventional recurrence marker, CA125, is widely used for follow-up after resection of OC, but CA125 has a long half-life in blood and lacks dynamic responses to tumor recurrence. Recent developments in liquid biopsy procedures are expected to overcome the difficulties in early diagnosis of OC recurrence after surgery. We applied droplet digital PCR (ddPCR) technology to detect circulating tumor-derived DNA in OC patients’ plasma during follow-up. Exome sequencing of 11 tumor–normal pairs of genomic DNA from consecutive OC patients identified tumor-specific mutations, and ddPCR probes were selected for each sample. Six of 11 cases showed apparent recurrence during follow-up (mean progression-free survival was 348.3 days) and all six cases were positive in ddPCR analyses. In addition, ddPCR became positive before increased plasma CA125 in five out of six cases. Increased allele frequency of circulating tumor DNA (ctDNA) is associated with increased tumor volume after recurrence. ddPCR detected ctDNA signals significantly earlier than increased CA125 in the detection of OC recurrence by imaging (49 days and 7 days before, respectively: p < 0.05). No ctDNA was detected in the plasma of recurrence-free cases. Our results demonstrate the potential of identifying ctDNA by ddPCR as an early detection tool for OC recurrence.
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一项开放标签，随机的II期试验，评估具有或不使用贝伐单抗的护理标准的功效和安全性卵巢癌：日本妇科肿瘤学组研究JGOG3023的基本原理，设计和方法。
影响因子：
3.8
作者：
Shoji T;Komiyama S;Kigawa J;Tanabe H;Kato K;Itamochi H;Fujiwara H;Kamiura S;Hamano T;Sugiyama T;Japanese Gynecologic Oncology Group
通讯作者：
Japanese Gynecologic Oncology Group
影响因子：
15.8
作者：
Parkinson CA;Gale D;Piskorz AM;Biggs H;Hodgkin C;Addley H;Freeman S;Moyle P;Sala E;Sayal K;Hosking K;Gounaris I;Jimenez-Linan M;Earl HM;Qian W;Rosenfeld N;Brenton JD
通讯作者：
Brenton JD
DOI：
10.1038/nrc4019
发表时间：
2015-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Bowtell DD;Böhm S;Ahmed AA;Aspuria PJ;Bast RC Jr;Beral V;Berek JS;Birrer MJ;Blagden S;Bookman MA;Brenton JD;Chiappinelli KB;Martins FC;Coukos G;Drapkin R;Edmondson R;Fotopoulou C;Gabra H;Galon J;Gourley C;Heong V;Huntsman DG;Iwanicki M;Karlan BY;Kaye A;Lengyel E;Levine DA;Lu KH;McNeish IA;Menon U;Narod SA;Nelson BH;Nephew KP;Pharoah P;Powell DJ Jr;Ramos P;Romero IL;Scott CL;Sood AK;Stronach EA;Balkwill FR
通讯作者：
Balkwill FR
影响因子：
46.9
作者：
Frampton GM;Fichtenholtz A;Otto GA;Wang K;Downing SR;He J;Schnall-Levin M;White J;Sanford EM;An P;Sun J;Juhn F;Brennan K;Iwanik K;Maillet A;Buell J;White E;Zhao M;Balasubramanian S;Terzic S;Richards T;Banning V;Garcia L;Mahoney K;Zwirko Z;Donahue A;Beltran H;Mosquera JM;Rubin MA;Dogan S;Hedvat CV;Berger MF;Pusztai L;Lechner M;Boshoff C;Jarosz M;Vietz C;Parker A;Miller VA;Ross JS;Curran J;Cronin MT;Stephens PJ;Lipson D;Yelensky R
通讯作者：
Yelensky R
影响因子：
14.9
作者：
Tate JG;Bamford S;Jubb HC;Sondka Z;Beare DM;Bindal N;Boutselakis H;Cole CG;Creatore C;Dawson E;Fish P;Harsha B;Hathaway C;Jupe SC;Kok CY;Noble K;Ponting L;Ramshaw CC;Rye CE;Speedy HE;Stefancsik R;Thompson SL;Wang S;Ward S;Campbell PJ;Forbes SA
通讯作者：
Forbes SA