血液循环肿瘤DNA测序技术在卵巢癌诊断中的可行性分析

Feasibility analysis of circulating tumor dna sequencing technology in ovarian cancer diagnosis

目的探究卵巢癌(OC)患者肿瘤组织与血液循环肿瘤DNA(ctDNA)驱动基因突变频谱改变的一致性,评估血液ctDNA测序技术在OC诊断中的可行性。方法选取2019年6月至2021年6月于呼和浩特市第一医院明确诊断的30例OC患者作为研究对象,采集所有患者术前外周血及肿瘤组织样本,检测ctDNA基因突变序列,分析肿瘤组织与血浆中ctDNA突变基因检测结果及肿瘤组织与血浆ctDNA驱动基因突变频率一致性。结果30例OC患者,肿瘤组织ctDNA驱动基因突变频率较高的前5位分别为MAP3K1框内缺失突变、DCP1B框内插入突变、AHNAK错义突变、TP53错义突变、ZNF331错义突变;血液ctDNA驱动基因突变频率较高的前5位分别为DCP1B框内插入突变、MAP3K1框内缺失突变、AHNAK错义突变、ZFHX3多重突变、PLEC错义突变。肿瘤组织及血液样本共涉及驱动基因173个,突变频率较高的基因共52个;肿瘤组织与血液样本中DCP1B、MAP3K1、CLTCL1、GRIN3A、ERBB2、MEGF6、MN1、ZFHX3、PLEC等多个基因突变频率高度一致,TP53、RANBP17、PDGFB、FES、TRIP11、TET2等基因在肿瘤组织样本中突变频率较高,而SLC34A2、NFATC2、TFEB、NCOA3等基因在血浆样本中突变频率较高。结论血浆和肿瘤组织样本均可检出ctDNA基因突变,二者可相互补充,且基因突变频谱具有较高一致性,可全面监控OC基因频谱在致病过程中的变化,有助于指导临床及时调整治疗方案。

Objective To explore the consistency of tumor tissue and blood circulating tumor DNA(ctDNA)driver gene mutation spectrum changes in patients with ovarian cancer(OC),and to evaluatefeasibility of blood ctDNA sequencing technology in the diagnosis of OC.Methods 30 patients with OC clearly diagnosed in Hohhot First Hospital from June 2019 to June 2021 were selected as the study subjects,and preoperative peripheral blood and tumor tissue samples of all patients were collected,ctDNA gene mutation sequence was detected,and ctDNA mutation gene detection results in tumor tissue and plasma were analyzed,as well as the consistency of ctDNA driver gene mutation frequency between tumor tissue and plasma.Results In 30 OC patients,the top 5 ctDNA driver gene mutations with high frequency were MAP3K1 in-frame deletion mutation,DCP1B in-frame insertion mutation,AHNAK missense mutation,TP53 missense mutation,and ZNF331 missense mutation.The top 5 ctDNA driver gene mutations with high frequency were DCP1B in-frame insertion mutation,MAP3K1 in-frame deletion mutation,AHNAK missense mutation,ZFHX3 multiple mutation,and PLEC missense mutation.There were 173 driver genes involved in tumor tissue and blood samples,and 52 genes with high mutation frequency.The mutation frequencies of DCP1B,MAP3K1,CLTCL1,GRIN3A,ERBB2,MEGF6,MN1,ZFHX3,PLEC and other genes in tumor tissue and blood samples were highly consistent,TP53,RANBP17,PDGFB,FES,TRIP11,TET2 and other genes had a high mutation frequency in tumor tissue samples,while SLC34A2,NFATC2,TFEB,NCOA3 and other genes had a high mutation frequency in plasma samples.Conclusion ctDNA gene mutation can be detected in both plasma and tumor tissue samples,and the two can complement each other,and the gene mutation spectrum has a high consistency,which can comprehensively monitor the change of OC gene spectrum in the pathogenesis process,and help guide clinical timely adjustment of treatment plan.