Application Of Circulating Tumor DNA Technology In Diagnosis And Treatment Of Ovarian Cancer

Objective In this study,next-generation sequencing(NGS)techniques were used to sequence and analyze circulating tumor DNA(ct DNA)in plasma of OC patients.According to the data obtained,the Ovarian Cancer(OC)high frequency mutation gene was analyzed statistically and the related pathways were enriched.To investigate the consistency between plasma ct DNA and DNA gene mutations in tumor tissues,and to explore whether ct DNA detection may replace tissue biopsy as an early detection and screening tool for OC in the future.Methods We screened 30 patients with OC admitted to the third level hospital of Hohhot,Inner Mongolia.The venous blood of the patients before treatment was collected,the plasma was extracted,and the ct DNA was purified and extracted.At the same time,the fresh OC tissue samples matching the same period were taken.Whole exome sequencing(WES)and bioinformatics analysis of ct DNA and fresh frozen tissue samples using NGS technique.SPSS24.0 statistical software was used to analyze the mutation of plasma ct DNA and tissue samples,and the final ct DNA was compared with the matched gene mutation profiles in tumor tissues and analyzed for consistency,the mutation of ct DNA and matched tumor tissue DNA at the same time was analyzed by transverse comparison.Results(1)Plasma ct DNA and NGS sequencing data were obtained from 30 cases of OC patients,and the average sequencing depth was 200 X.(2)OC mutation in two classes of samples the main mutation types is missense mutation,main mutation spectrum is C>T/G>A.The characteristics of SNP and Indel in the two types of samples were basically the same,and the heterozygote genotype showed more.(3)The consistency rate of susceptibility gene test results of the two types of samples was 93.3%,the sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of ct DNA in the study of susceptibility gene mutation were 96.4%,50%,96.4%,50%,kappa value = 0.464 > 0.4,P = 0.011 < 0.05,the detection of susceptibility genes of plasma ct DNA and tumor tissue DNA has good consistency.The study in the OC susceptible gene mutations(Germ)BPTF,NCOR2,NOTCH1 in plasma ct DNA and tumor tissue DNA mutation rate is higher.(4)Two types of sample driver genetic testing result consistent rate was 83.3%,ct DNA test driver mutations in the study of the sensitivity of 91.7%,specificity of 50%,PPV of 60%,and NPV of 88%,Kappa value = 0.444 > 0.4,P = 0.014 < 0.05,the ct DNA and tumor tissue DNA driver better consistency of genetic testing.30 cases of OC high-frequency mutations in the tumor tissue samples average mutation rate is 89.2%;In the ct DNA mutation rate is 86.3% on average.(5)The results of general data analysis showed that there was no significant association between OC drive gene mutation and age and clinicopathologic features(tumor stage,CA125 value)(P> 0.05).(6)High frequency mutation gene and driving mutation gene MAP3K1 and AHNAK had high mutation rate in two kinds of samples,MAP3K1 more enrichment in the MAPK signaling pathway.Conclusions(1)Plasma ct DNA gene mutation spectrum and matches the DNA of the tumor tissue spectrum is the same,the main mutation spectrum is given priority to with C>T/G>A,the study found that two types of samples the main mutation types is given priority to with missense mutation.(2)In this study,the OC susceptibility genes(germline mutation)BPTF,NCOR2 and NOTCH1 have a high mutation rate in plasma ct DNA and tumor tissue DNA.Their abnormal expression is related to the occurrence of OC and is expected to become biomarkers and therapeutic targets of OC.(3)In this study,high frequency mutation gene and driving mutation gene MAP3K1 and AHNAK were found to have high mutation rates in the two types of samples,suggesting that MAP3K1 and AHNAK proteins may be biomarkers of OC occurrence.The high frequency mutant gene MAP3K1 is mainly enriched in MAPK signal pathway,suggesting that MAP3K1 may be associated with OC malignant proliferation.(4)The plasma ct DNA of OC patients had a good consistency with the DNA gene mutation of matched tumor tissues and had a high sensitivity,it is suggested that ct DNA stems from tumor tissue and carry the genetic mutation information is consistent with the tumor tissue;ct DNA analysis(liquid biopsy)is a promising alternative to tissue biopsy and may be used as a tool for early detection and screening of OC.