| Gastric cancer(GC)is already the fourth most common diagnosed cancer in the world and the second most fatal cancer in the world.In China,GC is the third most common cause of cancer and cancer deaths in both sexes,and the incidence of gastric cancer in China is gradually increasing.Since the early diagnosis of gastric cancer is difficult,the survival rate is always low,and most patients have late unresectable or metastatic lesions at the time of diagnosis.Therefore,the overall clinical outcome of GC patients is still poor,and the 5-year survival rate is lower than 30%.The discovery of new biomarkers and their use in combination with the diagnosis,staging,and prognosis of traditional cancers will help improve the early diagnosis of GC and the care of patients.In particular,the discovery of biomarkers capable of early identification of tumor cells and predicting therapeutic response can greatly improve the therapeutic effect of GC.The interferon regulatory factor 4 binding protein(IBP)is a protein that can be screened from the human lymph node c DNA library by the Pernis team in 2002 through a yeast two-hybrid technique to bind IRF-4.It is mainly expressed on T lymphocytes and plays an important role.IBP is a highly conserved protein in vertebrates with a molecular weight of about 75 Kd.The coding gene is located on chromosome 6p21.31.It is highly homologous to SWAP-70.SWAP-70 plays an important role in B cell activation and Ig subclass transformation.IBP is called It is a novel guanine nucleotide exchange factor(GEF).GEFs are members of the Dbl protein family and represent regulatory factors for the activation state of major Rho GTPases.Rho GTPases play an important role in many biological processes,including regulation of cytoskeletal organization,cell cycle progression,and transduction of signals from extracellular environments.They have also been shown to contribute to pathological processes such as cancer cell migration,invasion and metastasis.In addition,Rho GTPases have oncogenic activity,which is associated with increased expression and activity in various cancers,and related reports also indicate that IBPs exhibit GEF activity against Rho family GTPases including Rac1,Cdc42,and Rho A.The human p53 gene is about 20 kb in length and has 11 exons and introns.It is located in the 17 th short arm of human chromosome.It has both wild-type and mutant genotypes.Its products also have mutant p53 protein and wild-type p53 protein.Two kinds,wild-type p53 gene can regulate cell growth and apoptosis,and is a tumor suppressor gene.The product p53 protein is an anti-cancer factor,and its moderate expression can regulate the normal growth and development of cells,but the deletion of its coding gene and The mutant p53 protein produced by the mutation is positively correlated with the development of many tumors,and the available data indicate that it is a cancer-promoting factor.Because the wild-type p53 protein has a short half-life and is difficult to detect,and the mutant p53 protein has a property of being difficult to hydrolyze due to loss of function,and often accumulates in cells,the detection of p53 protein by immunohistochemistry is generally a mutation type(In this paper,the mutation type p53 is detected,and the following unspecified is referred to as p53).Mutations in the p53 gene have been reported to be associated with up to 50% of malignant tumor patients.In gastric cancer,the p53 gene is one of the most mutated tumor suppressor genes,and its gene mutations and product overexpression can occur at various stages of the tumor.In recent years,the research team led by Prof.Hu Chuanqi found that IBP is highly expressed in colon cancer and breast cancer and plays an important role.It is found that IBP is negatively correlated with the expression of mutant p53 protein in breast cancer specimens.Further studies have found that IBP is a novel target gene of p53 protein(wild type).Increased expression of p53 can inhibit the expression of IBP,while induction of IBP is associated with inhibition of p53.In breast cancer cell lines,wild-type p53 can bind to the IBP promoter.Recent studies have also found that IBP plays an important role in tumors such as oral squamous cell carcinoma and human salivary adenoid cystic carcinoma.However,the expression of IBP in GC has not been reported.Therefore,this study firstly detected the expression of IBP in gastric adenocarcinoma cell lines by immunofluorescence,Real-time PCR and Western blot,and preliminary analysis of IBP in gastric adenocarcinoma cells.Expression pattern.Then,immunohistochemical staining was used to detect the expression of IBP and p53 protein in human gastric adenocarcinoma tissue samples,and to explore the relationship between IBP and p53 protein expression and clinicopathological features in GC.The main experimental contents,results and conclusions are as follows:1.Immunofluorescence assay showed that IBP was mainly expressed in the cytoplasm and membrane of gastric adenocarcinoma cell line MKN-45.Immunoblotting and Real-Time PCR confirmed the expression of IBP in gastric adenocarcinoma cell line MKN-45 and SGC-7901.MKN-45 expression was higher than that of SGC-7901 cells,and the difference in malignancy between the two cells was associated.IBP appeared to have a tendency to be expressed in gastric cancer cells with higher malignancy.2.In this experiment,150 cases of HE-slices of gastric adenocarcinoma confirmed by pathology of our hospital were collected.Immunohistochemical En Vision staining showed that the positive expression rate of IBP was higher than that of non-gastric adenocarcinoma group,the difference was statistically significant(P<0.05),and also confirmed that IBP is expressed in the membrane and cytoplasm of patients with gastric adenocarcinoma,which is brown-yellow particles.The positive expression of IBP was correlated with the pathological grade of the patients(P<0.05),and there was no correlation with the age,gender,depth of invasion of the stomach wall,TNM stage,Lauren classification and tumor location(P>0.05),indicating that IBP was The occurrence and development of GC plays an important role.In connection with the cell experiment in the first step,we speculate that overexpression of IBP will promote the development of tumors and stimulate the development of tumor cells to poor differentiation and malignancy.Overexpression of IBP suggests that the patient’s prognosis is poor,making it an important indicator of GC prognosis,but further case follow-up verification is needed.3.We also detected the expression of mutant p53 protein in 150 specimens by immunohistochemical En Vision method.The positive expression rate of p53 protein in 150 specimens was higher than that in non-gastric adenocarcinoma group.The difference was statistically significant(P<0.05),p53 protein is mainly expressed in the nucleus and is brownish yellow or tan particles.At the same time,statistical analysis showed that the positive expression of p53 protein was correlated with age,gender,pathological grade and Lauren classification(P<0.05),and had no correlation with the depth of gastric wall invasion,TNM stage and tumor location(P>0.05).Then,Spearman rank correlation was used to analyze the correlation between IBP and p53 protein.The results showed that there was no significant correlation between the expression of IBP and the expression of p53 protein in gastric adenocarcinoma tissues,and the difference was not statistically significant(r =0.013,P>0.05),which seems to contradict the clinical pathology of IBP and gastric adenocarcinoma,but the occurrence and development of gastric adenocarcinoma is a multi-step multi-step process involving multiple pathological pathways and complex relationships between various tumor factors..Moreover,there are many mutants of mutant p53 protein in gastric adenocarcinoma,and a single p53 antibody cannot accurately reflect the expression of the entire mutant p53 protein.Therefore,further molecular pathology studies are needed regarding the detailed relationship between p53 protein and IBP. |
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