| Objective:To compare the overall genetic consistency of peripheral blood circulation tumor DNA and histological detection genes in patients with advanced gastric cancer and the consistency of each gene.To discuss the significance of peripheral blood circulation tumor DNA in patients with advanced gastric cancer.Methods:Solid tissue and plasma specimens from 30 patients with advanced and newly diagnosed gastric cancer were collected,the histological gene status and the genetic status of ctDNA in peripheral blood of 30 patients with advanced gastric cancer were detected through next generationg sequencing(NGS)technology.Taking histological gene status as the gold standard,and histological gene status and ctDNA as the actual situation of patients,comparison and analysis of the comparability of peripheral blood ctDNA,sensitivity,specificity,consistency.Taking histological gene status as the gold standard and histological gene status and ctDNA as the actual situation of patients,the comparability,sensitivity,specificity and consistency of EGFR,HER2,TP53,PIK3CA,KRAS,SMAD4 and other single genes in ctDNA were compared and analyzed,and the significance was discussed.The difference of mutation abundance of related genes and its significance were studied.Results:1.All patients have detected related gene mutation,and detected by histological specimens in biomarkers,at least one of them is detected in ctDNA,Six patients were found to have identical genes in the two samples,usually for one or two,mainly for the TP53,among the identical mutated genes in the two tests,the mutation abundance showed higher mutation abundance in histological specimens.It was also found that when only one gene mutation was detected in tissue samples,9 cases were detected,and the results of genes detected in ctDNA and histological samples were the same in 6 cases,still mainly TP53.Among the patients with inconsistent mutant genes,15 cases had more genes detected in histological samples than ctDNA,9 cases had more mutations detected in ctDNA than histological samples,and 138 mutations were detected in 30 patients,71 in histological samples and 67 in ctDNA.2.The genes detected in histological specimens are the gold standard,and all the genes detected in histological specimens and ctDNA are the real results;In a single patient,if the gene detected in the tissue was completely consistent with all the detected genes,the tissue was positive;if the gene detected in the ctDNA was completely consistent with all the detected genes,the ctDNA was positive;19 cases were histologically positive,and 10 cases were ctDNA positive.Among them,there was a difference in the observation results.?~2was 4.76,P<0.05,suggesting that the positive detection rate of the two was different.Whether the test results are related or not,which was calculated as P=1 and P>0.05,indicating that there was no correlation between them.The sensitivity of ctDNA was 31.5%,specificity was 63.6%,coincidence rate was43.3%,misdiagnosis rate was 36.4%,missed diagnosis rate was 68.5%,diagnostic index was 0.95,Youden index was-0.0.5,positive likelihood ratio was 0.865,negative likelihood ratio was 1.07,positive predictive value was 60%,negative predictive value was 35%.3.Among them,the most common mutation was TP53,29 cases out of 30 patients were positive,28 cases out of histological samples were positive,26 cases out of ctDNA was positive,and 25 cases were positive for both.Followed by PIK3CA,30 cases,16cases were positive,8 cases of histological sample is positive,positive ctDNA in 15 cases,and 7cases were both positive,ctDNA detection sensitivity was 87.5%,the specific degree is 63.6%,consistent rate was 70%,the misdiagnosis rate was 36.4%,the missed diagnosis rate was 12.5%,the diagnostic index of 1.511,Youden index is 0.511,positive likelihood ratio is 2.4,the negative likelihood ratio is 0.196,positive predictive value was46.7%,negative predictive value of 93.3%;The sample size n<40,Fisher's exact test value P=0.035,so P<0.05,the two can be considered to be related,the calculated correlation coefficient phi is 0.452,Cramer V is 0.452,Pearson R is 0.452,Spearman correlation is 0.452,the two are considered to have a certain correlation.HER2 was next,and 8 cases of the 30 patients were positive,including 5 cases in histological samples,4cases in ctDNA,and 1 cases in both.Secondly,KRAS was found to be positive in 8cases out of 30 patients,including 4 cases in histological samples,6 cases in ctDNA and2 cases in both.SMAD4 was followed,and 8 cases of the 30 cases were positive,including 6 cases in histological samples,3 cases in ctDNA,and 1 cases in both.Secondly,EGFR was found to be positive in 5 cases of 30 patients,including 4 cases in histological samples,4 cases in ctDNA and 3 cases in both.PIK3CA mutation was found in 4 cases of the 5 EGFR mutants.In patients with PIK3CA mutation,other coexisting oncogene mutation sites included 2 cases of KRAS,2 cases of BRAF,and 4 cases of EGFR.HER2 is also accompanied by PIK3CA mutation,including 4 cases in solid tissue and 4 cases in ctDNA,and KRAS mutation was also found in 3 patients with HER2.4.In terms of mutation abundance,the detection abundance of TP53 in histology was mostly higher than that in ctDNA,and the detection abundance of TP53 in ctDNA was higher than that in histology in 4 cases.Among them,the abundance of PIK3CA detected only in histology was higher than that of patients detected only in ctDNA,and all of them were greater than 1.The detection abundance of PIK3CA in ctDNA was only lower than 1,while in histology and ctDNA,the detection abundance was greater than 1in 4 cases and less than 1 in 3 cases.The detected mutation abundance in histology of Kras was greater than that in ctDNA,and the detected mutation abundance in histology of Kras was also greater than 1.The detection abundance of HER2 in histology was mostly higher than that in ctDNA,which was greater than 1 in histology and less than 1in ctDNA.The detection abundance of EGFR in histology was mostly higher than that in ctDNA,and the detection abundance in histology and ctDNA was greater than 1.Conclusions:1.CtDNA detection is poor in sensitivity and consistency in advanced gastric cancer,which is not as valuable as solid tissue biopsy at present,but still has a high specificity and can be used as an alternative for patients with advanced gastric cancer who cannot obtain tissue samples.2.For the detection of a single gene,the detection rate of PIK3CA in ctDNA is better than that in histological samples.When HER2 is tested,ctDNA test can be added to find more HER2 mutation patients.When EGFR testing was performed,ctDNA testing was added to detect more EGFR mutation patients.3.Multiple gene mutations were found in patients with gastric cancer through ctDNA,which may provide more possibilities for specific molecular targeted therapy.4.The mutation abundance of the same gene detected in solid tissues was mostly higher than that of ctDNA. |
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