Association Between TP53,HER2 Gene Mutation And The Over-expression Of Protein And Clinicopathological Features In Gastric Cancer

Objective:Tumor suppressor gene TP53 and proto-oncogene HER2 play an important role in the pathogenesis of gastric cancer.Although there are many related reports in the past,there are few reports about whether the mutation of TP53,HER2 gene is consistent with the abnormal expression of its protein,and whether the gene mutation and the clinicopathological features of gastric cancer.In this study,exon 5,7,8 of TP53 gene and exon13,22-24,25-26 of HER2 gene were sequenced in gastric cancer and para-cancerous control tissues,and immunohistochemical staining of p53 and HER2 proteins were performed to compare and analyze the relationship between the mutation and overexpression of these two genes and the pathogenesis and clinicopathological features of gastric cancer,so as to understand the occurrence and development of gastric cancer and provide theoretical basis for Circulating Tumor DNA(ct DNA)to early diagnosis and clinical application of gastric cancer Methods:The data of 76 cases of gastric cancer who underwent surgery in the Department of Gastrointestinal surgery of the first Hospital of Jilin University from January 2018 to January 2019 were collected.With the informed consent of their families,tissue samples were collected after operation.DNA was extracted from gastric cancer and para-cancerous tissues.TP53 gene exons 5,7,8 and HER2 gene exons 13,22-24,25-26 were amplified and electrophoretic by polymerase chain reaction(polymerase chain reaction,PCR).DNA was recovered by cutting glue and sequenced by Sanger sequencing method.The BLAST tool in NCBI was used to compare the sequencing results with the database,and the DNAMAN version6 software was used to analyze the gene mutation.P53 and HER2 protein immunohistochemical staining was performed with monoclonal antibody.The gene mutation,protein overexpression and clinicopathological features of gastric cancer were compared and analyzed by SPSS24.0 software,and their correlation was analyzed.Results:1.About TP531).The total number of TP53 gene mutations in gastric cancer was 29,including 69%(20/29)missense mutations,10.3%(3/29)synonymous mutations and20.7%(6/ 29)frameshift mutations.The total mutation rate of TP53 gene in gastric cancer tissue and para-cancerous tissue was 39.2%(29/74)and 8.1%(6/74)respectively.The mutation rate of TP53 gene in gastric cancer tissue was significantly higher than that in para-cancerous tissue(P=0.035).The mutation rates of exon5,exon 7 and exon 8 were 21.6%(16/74)and 2.7%(2/74),14.9%(11/74)and 2.7%(2/74)and 16.2%(12/ 74)and 2.7%(2/74)respectively(P=0.001;P= 0.005;P=0.009).No significant association was found between TP53 gene mutation and pathological stage,Lauren classification,degree of differentiation,size,neurovascular invasion and lymph node metastasis of gastric cancer2).The overexpression rate of p53 protein in gastric cancer was 51.4%.The negative expression rate of p53 protein was 48.6%.No significant correlation was found between overexpression of p53 protein and pathological stage,Lauren classification,degree of differentiation,size,neurovascular invasion and lymph node metastasis of gastric cancer3).The mutation rate of exon7 in p53 overexpression group was 23.7%(9/38),which was significantly higher than that in p53 negative expression group(5.6%,2/36)(P= 0.035).At the same time,the overexpression rate of p53 protein in exon7 mutation group was 81.8%(9 / 11),which was significantly higher than that in non-mutation group(46.0%,29/63)(P= 0.035)2.About HER21).The total number of HER2 gene mutations in gastric cancer was 14.The missense mutation rate was 50.0%(7/14),synonymous mutation rate was 35.7%(5/14),and frameshift mutation rate was 14.3%(2/14).The total mutation rate of HER2 gene in gastric cancer and para-cancerous tissues was 18.9%(14/74)and 2.7%(2/74)respectively.The mutation rate of HER2 gene in gastric cancer was significantly higher than that in para-cancerous tissues(P=0.013).The mutation rates of exon25-26 were 14.9%(11/74)and 1.4%(1/74)respectively,the mutation rate in gastric cancer tissue was significantly higher than that in para-cancerous tissue(P = 0.003);The mutation rates of exon22-24 were 8.1%(6/74)and 1.4%(1/74)respectively,and there was no significant difference between the two groups(P=0.177).Exon13 mutations were not detected in gastric cancer tissues and para-cancerous tissues.The mutations in exon 22-24,25-26 of HER2 gene were not significantly associated with pathological stage,Lauren classification,degree of differentiation,size,neurovascular invasion and lymph node metastasis of gastric cancer2).The overexpression rate of HER2 protein in gastric cancer was 29.7%,and the negative expression rate was 70.3%.The overexpression rate of HER2 protein in intestinal type was 55.0%(11/20),which was significantly higher than that in mixed type(28.1%,9 /32)and diffuse type(9.1%,2.22)(P=0.035)3).There was no significant correlation between overexpression of HER2 protein and mutations in exon 22-24 and 25-26 of HER2 gene(P > 0.05)Conclusion:1.The mutations of TP53 and HER2 genes in gastric cancer suggesting that they are associated with the pathogenesis of gastric cancer,while the mutations in the main exons of TP53 and HER2 genes are not related to pathological stage,Lauren classification,degree of differentiation,size,neurovascular invasion and lymph node metastasis of gastric cancer2.The overexpression of HER2 protein is related to Lauren classification of gastric cancer,while the overexpression of p53 protein is not related to pathological stage,Lauren classification,degree of differentiation,size,neurovascular invasion and lymph node metastasis of gastric cancer.3.In gastric cancer,the mutation of TP53 gene,the detection of exon7 mutation of TP53 gene could reflect the overexpression of p53 protein.The mutation of TP53 gene and p53 protein overexpression had a consistent trend,but no significant correlation was found between the mutation of HER2 gene and the overexpression of HER2 protein.