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Application And Prognostic Analysis Of NGS In Clinical Diagnosis And Treatment Of Gastric Cancer

Posted on:2021-01-22Degree:MasterType:Thesis
Country:ChinaCandidate:M L PuFull Text:PDF
GTID:2404330602473547Subject:Surgery
Abstract/Summary:PDF Full Text Request
Background and ObjectiveGastric cancer is one of the common malignancy in the world.Most patients are diagnosised at the advanced stage,because the symptoms of early gastric cancer are not obvious.The prognosis of advanced gastric cancer is poor,with a 5-year survival rate of less than 10%.The existing research on the mechanism of gastric cancer metastasis and related factors of poor prognosis is still unclear,the main reason is that malignant tumors are highly heterogeneous.Tumor heterogeneity is not only reflected in age,gender,region,etc,but also the molecular level of gastric cancer genes are differences.In the era of individual cancer treatment and precision medicine,the traditional histopathological classification is limited clinical therapy in many ways,which reflecting the inherent characteristics of tumors.With the development of biotechnology,the application of Next Generation Sequencing Panel Test(NGS)in clinical practice has also become popular.According to the genotype we can use genetic testing to divide gastric cancer into multiple subtypes to guide the early diagnosis and personalized treatment of the disease.Therefore,single genes related to the prognosis of gastric cancer at the molecular level is of great significance for clinical treatment and prognosis of patients.The high-throughput gene sequencing method used by NGS can effectively identify sequence mutations related to genetic diseases,while the traditional Sanger sequencing method only detect single or a fraction of genes.When whole-genome sequencing research methods are used to detect a large number of genes,NGS technology makes such tests less expensive.More importantly,NGS has a higher accuracy rate than traditional single-gene sequence analysis in the diagnosis of diseases involving multiple different genes.At present,the molecular typing of gastric cancer is still very limited in clinical applications.This situation makes clinicians have limited choices for individualized treatment options for patients with gastric cancer,and it is difficult to significantly improve the treatment effect of gastric cancer.Therefore,the use of NGS technology can establish the gastric cancer gene profile and the development of related targeted drugs.In order to study the significance of NGS in the occurrence and development of gastric cancer,clinical diagnosis and treatment and prognosis analysis.Therefore,this article aims to analyze the relationship between the relevant genes and clinical pathological characteristics and survival time of gastric cancer patients detected by NGS technology.MethodsA retrospective analysis was performed on 116 patients who underwent radical gastrectomy in Zhengzhou University First Affiliated Hospital from February 2018 to April 2019.The postoperative pathology was clear and NGS detection was performed.We divide genes into four groups according to their functions.The gene test results of the above patients are selected to analyze the differences between gene mutations and clinicopathological characteristics and gene expression.The t test was performed on the age,the largest tumor diameter regional and lymph node positive rate of patients with gastric cancer,the ?2 test was performed on gender,smoking,alcohol consumption,nerve and vascular invasion,and gene mutation rate.The degree of differentiation,tumor stage was analyzed by rank sum.After surgery,the disease-free survival(DFS)of patients was Kaplan-Meier to describe the survival curve,P<0.05 is considered statistically significant.Results1.There is a difference in gender of TP53 gene,and the difference is statistically significant(P<0.05),TP53 gene is affected by age,smoking history,drinking history,tumor differentiation,TNM stage,lymph node positive rate,nerve and vascular invasion are differences.The differences are not statistically significant(P>0.05).The differences between the ERBB2 gene mutation group and the wild-type group in age,sex,smoking history,drinking history,degree of differentiation,TNM staging,lymph node positive rate,and neurovascular invasion is not significant.None are statistically significant(P>0.05).2.The mutation status of CYP2D6 gene is statistically significant in the positive rate of lymph nodes and nerve invasion(P<0.05);CYP2D6 gene is differences in the mean age,gender,smoking history,drinking history,tumor differentiation degree,TNM stage,tumor maximum diameter and neurovascular invasion.There is no statistical significance(P>0.05).The differences between CYP3A5 gene mutation group and the wild-type group in smoking history,drinking history,lymph node positive rate,nerve invasion,and vascular invasion are statistically significant(P<0.05);There is no statistical significance in the age mean,gender,tumor differentiation,TNM stage,largest tumor diameter(P>0.05).The differences between the CDA gene mutation group and the wild-type group in drinking history are statistically significant(P<0.05);there are no statistic significance on CDA gene in age mean,gender,smoking history,tumor differentiation,TNM stage,nerve and vascular invasion,and tumor maximum diameter(P>0.05).3.There is no significant difference between the ERCC2 gene mutation group and the wild-type group in age,gender,smoking history,drinking history,tumor differentiation,TNM stage,lymph node positive rate,vascular invasion,and tumor diameter(P>0.05).There is no significant difference between the XRCC1 gene mutation group and the wild-type group in age,gender,smoking history,drinking history,tumor differentiation,TNM stage,lymph node positive rate,vascular invasion,and tumor diameter(P>0.05).4.MTHFR gene is different in age,and the difference is statistically significant(P<0.05);MTHFR gene between gene mutation group and the wild-type group is different in gender,smoking history,drinking history,tumor differentiation degree,TNM staging,lymph node positive rate,vascular invasion,the largest tumor diameter(P>0.05).In NQO1 gene,there are no significant differences between gene mutation group and the wild-type group in the mean age,gender,smoking history,drinking history,tumor differentiation,TNM stage,lymph node positive rate,vascular invasion,and maximum tumor diameter(P>0.05).5.The median DFS of 116 patients is 19 months.The DFS of the TP53 gene is different between the two groups,and the difference is statistically significant(P=0.03).The median DFS of the ERBB2 gene in the mutant group and the wild-type group is not statistically significant(P=0.40).There are no significant differences in the mutation status of CYP2D6 gene,CYP3A5 gene,and CDA gene on DFS(P>0.05).There are no significant differences in the mutation status of ERCC2 gene and XRCC1 gene on DFS(P>0.05).NQO1 gene had a difference in DFS between the two groups,and the difference is statistically significant(P=0.03);MTHFR gene had no difference in DFS between the two groups(P=0.59).Conclusions1.Among proto-oncogenes and tumor suppressor genes,the mutation rate of TP53 gene differs between genders,and the mutation rate of male patients is higher than that of female patients.2.Among the related genes in drug metabolism enzymes,the positive rate of lymph nodes in the CYP2D6 gene mutation group and the wild group is different,and the mutation rate of mutation group is higher than the wild group,the mutation rate is different between the nerve invasion,and the mutation rate of which has not occurred invasion is higher than that of nerve invasion.The CYP3A5 gene mutation group and the wild group have different in lymph node positive rates,and the rate of mutation group is higher than the wild group,the mutation rate is different in the patients'smoking history,drinking history,nerve and vascular invasion.Compared with the positive factor groups,the negative factor groups have higher mutation rate.The mutation rate of CDA gene is different in drinking history,and the mutation rate of drinking patients is higher than that of patients without drinking history.3.Among the genes related to DNA repair,the two groups of ERCC2 gene and XRCC1 gene can not be considered to be different in the patients' average age,positive rate of lymph nodes,and the largest tumor diameter.The two groups of ERCC2 gene and XRCC1 gene could yet be considered to have different mutation rates in clinical and pathological factors such as gender,smoking history,drinking history,tumor differentiation,TNM stage,nerve and vascular invasion.4.Among genes involved in biochemical reactions,the average age of the MTHFR gene mutant group is different from that of the wild group,and the average of wild group is higher than the mutant group.In the NQO1 gene,mutation group and wild group can not be considered different in average age,positive rate of lymph nodes,and the largest tumor diameter.NQO1 gene could yet be considered to have different mutation rates in clinical and pathological factors such as gender,smoking history,drinking history,tumor differentiation,TNM stage,nerve and vascular invasion.5.In the prognosis analysis of gastric cancer patients,the prognosis of the TP53 gene wild-type group is better than that of the mutant group,and the prognosis of the NQO1 gene mutant group is better than the wild-type group,the remaining genes cannot yet be considered to have different prognosis between the mutant group and the wild-type group.
Keywords/Search Tags:Gastric cancer, Gene, Next generation sequencing panel test, Disease-free Survival
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