Diagnosis Value Of Circulating Tumor DNA For Ovarian Cancer Based On High-throughput Sequencing Technology

BackgroundOvarian cancer is the cancer with the highest fatality rate among gynecological tumors,and currently there are limited screening and early diagnosis strategies.Circulating tumor DNA(ctDNA)carries tumor mutation information and has potential applications in the diagnosis and treatment of a variety of cancers.However,its role in the early diagnosis of ovarian cancer remains unclear.Materials&MethodsWe enrolled 54 patients with epithelial ovarian cancer and 50 patients with benign ovarian diseases.Detailed clinicopathological information was then collected.High-throughput targeted capture sequencing was conducted using a panel containing 338 cancer-related genes.Information about circulating free DNA(cfDNA)concentration and characteristics of ctDNA mutation profiles were collected.Logistic regression model were built combining characteristics of ctDNA and clinical data.ResultsA total of 16,8,and 30 FIGO ?,?,and ? ovarian cancer patients were enrolled,including 27 high-grade serous carcinomas.Control group included 9 cases of borderline ovarian tumors.The cfDNA concentration was not significantly different between the two groups(p=0.073),but stage ? and ? ovarian cancer had significantly higher level of cfDNA than stage ?(p=0.017).High-grade serous cancer had significantly higher level of cfDNA than non-high-grade serous cancer(p=0.006).The ctDNA somatic mutation was not detected in the control group.The overall detection rate in the case group was 85.2%,and 75.0%,87.5%,and 90.0%for stage ?,?,and ?,respectively.The mutation burdens of ctDNA were not related to stage and pathological type.However,a linear correlation was discovered between mutation burderns in the ctDNA and tissue(y=0.215x+1.235).The Kappa values of TP53,ARID1A,PIK3CA,KRAS in tissues and ctDNA were 0.82,0.82,0.71,and 0.92,respectively.The allele mutation frequency and ctDNA concentration of stage I ovarian cancer were significantly lower than those of stage ? and ?.The sensitivity and specificity of ctDNA somatic mutation were 85.2%and 100.0%,respectively.By combining with other indicators,the sensitivity could be improved,compared with ctDNA alone.However,the Youden index decreases.The sensitivity and specificity of ctDNA combined with cfDNA concentration,CA125,and imaging manifestations were 100.0%and 82.0%,respectively.The diagnostic sensitivity and specificity of ctDNA combined with cfDNA concentration and CA125 were 96.3%and 74.0%,respectively.ConclusionscfDNA concentration has no significant difference between ovarian cancer and ovarian benign diseases,but it still has the potential value to distinguish pathological types and tumor stages in ovarian cancer.The detection of ctDNA mutations in ovarian cancer is consistent with major tissue mutations to some extent.Allelic mutation frequency and ctDNA concentration are different in different pathological types and stages.ctDNA is not detected in benign ovarian diseases,and the detection rate is relatively high in ovarian cancer,especially among early ovarian cancer.The diagnostic specificity of ctDNA is extremely strong.Based on high-throughput targeted capture sequencing of ctDNA,combining indicators of ctDNA,cfDNA concentration,CA125 and imaging manifestations has high diagnostic value for ovarian cancer.