| Background and Objective Gastric cancer(GC)is one of the most common malignant tumors in the digestive tract.It ranks fifth in all cancers worldwide and its mortality rate ranks third.Gastric cancer is a highly heterogeneous disease,and its development is a multi-step,multi-stage complex process.At present,many studies at home and abroad have shown its pathogenesis associated with Helicobacter pylori(HP)infection,EB virus infection,genetic,physicochemical,diet and other factors,but the specific pathogenesis has not been fully elucidated.In recent years,with the development of molecular pathology and related research,it is found that the occurrence of gastric cancer is closely related to Microsatellite instability(MSI).MSI can directly or indirectly cause activation and tumor suppression of related oncogenes.The inactivation of the gene eventually leads to canceration.Microsatellites(MS)are repetitive short tandem DNA sequences.When a mismatch repair gene(MMR)is defective or mutated,the microsatellite sequence is prone to replication errors leading to MSI.Mismatch repair genes are a group of highly conserved genes whose function is to repair errors in DNA replication or damage,such as base mismatches,deletions,and insertions,and play an important role in maintaining the fidelity of DNA information transmission.Defects or abnormal changes in the MMR gene can cause genomic instability and accumulation of mutations,leading to the development of tumors.Studies have shown that MMR gene defects are the main mechanism of hereditary non-polyposis colorectal cancer.In other tumors such as endometrial cancer,lung cancer and gastric cancer,defects in MMR gene are also involved in tumor formation.The mismatch repair genes hMSH6 and hPMS2 are two important genes in the repair system that initiate the mismatch repair process of the cells.Studies have suggested that the loss of hPMS2 protein expression may play an important role in the development of solid,poorly differentiated adenocarcinoma in the stomach,and the detection of hMSH6 protein expression in gastric mucosa may contribute to gastric mucosal dysplasia and infiltration.Early identification of gastric cancer.The AT-rich sequence binding protein 2(SATB2)is a newly discovered transcription factor that binds to the nuclear matrix attachment region.The SATB2 protein is involved in gene recombination,chromatin remodeling,and cell differentiation.It plays a more important biological role in many processes,and has become a hot spot for researchers at home and abroad to explore its potential role in cancer development.Studies have shown that SATB2 is involved in the development of a variety of malignant tumors,including colorectal cancer,breast cancer,esophageal squamous cell carcinoma,oral squamous cell carcinoma,gastric cancer,osteosarcoma.For the mechanism of action of SATB2 protein in malignant tumors,the current literature indicates that SATB2 can be used as a tumor suppressor or a carcinogen.The reason may be that SATB2 protein can regulate different downstream in different types of tumor tissue cells.Gene expression,thereby exerting different biological effects.Studies have shown that SATB2 may play a role as a tumor suppressor gene in gastric cancer and may therefore become a potential new therapeutic target.However,how SATB2 protein plays a role in the development of gastric cancer,its related mechanisms or pathways have not been reported in related literature.Studies have reported that the loss of SATB2 expression in colorectal cancer is more likely to be observed in tumors with mismatch repair gene defects.Is there any loss of SATB2 protein expression in gastric cancer associated with mismatch repair gene-deficient tumors? Does the two play synergistic or completely irrelevant in the development of gastric cancer? At present,MMR gene hMLH1 and hMSH2 proteins are more studied in gastric cancer,and it is confirmed that it plays an important role in the occurrence and development of gastric cancer,but how do hMSH6 and hPMS2 proteins play a role in the development of gastric cancer,and whether there is any correlation between them.At present,there is no clear research report yet,and further research is needed.Therefore,this study intends to detect the expression of mismatch repair proteins hMSH6,hPMS2 and SATB2 in gastric cancer by immunohistochemistry,analyze the relationship between three proteins and their clinicopathological features,and further explore the mechanism of gastric cancer.Provide basic research data for the early diagnosis and treatment of gastric cancer.Material and Methods1.100 cases of paraffin-embedded specimens from patients with gastric cancer who underwent radical gastrectomy in the pathological diagnosis department of Kunming Jinyu Medical Laboratory Co,Ltd.from September 2015 to September 2017 were collected as experimental group;50 non-cancer stomachs were selected.Mucosal paraffin-embedded specimens were used as the control group of this experiment.2.Immunohistochemistry was used to detect the expression of hMSH6,hPMS2 and SATB2 proteins in 150 experimental specimens,and clinicopathological analysis was carried out under the guidance of senior pathologists.3.Statistical analysis: SPSS 17.0 statistical software package was used for data analysis.The relationship between hMSH6,hPMS2 and SATB2 protein expression and clinical pathological features was analyzed by counting data chi-square test,using Spearman linear correlation between the three.Correlation analysis was statistically significant at P < 0.05.Results1.Expression of hMSH6 protein in gastric cancer and its relationship with clinicopathological features1.1 The expression of hMSH6 protein was deleted in 9 out of 100 cases of gastric cancer,the deletion rate was 9%(9/100)and positive in 50 cases of non-cancerous mucosa.The deletion rate was 0%(0/50).There was a significant difference in the expression of hMSH6 protein between gastric cancer and non-cancerous mucosa(P=0.029).1.2 The expression of hMSH6 protein was not correlated with sex(P=0.493),age(P=0.355),differentiation degree(P>0.999),tumor size(P=0.727),vascular cancer thrombus(P>0.999),lymph node metastasis(P=0.112),depth of invasion(P=0.098),clinical TNM stage(P=0.469).2.Expression of hPMS2 protein in gastric cancer and its relationship with clinicopathological features2.1 hPMS2 protein was absent in 14 cases of 100 cases of gastric cancer,the deletion rate was14%(14/100),and it was positive in 50 cases of non-cancer mucosa.The deletion rate was0%(0/50),compared with hPMS2.The expression loss of protein in gastric cancer tissues and non-cancer mucosa tissues was statistically significant(P=0.013).2.2 The expression of hPMS2 protein and gender of gastric cancer patients(P=0.780),age(P=0.454),degree of differentiation(P=0.601),tumor size(P>0.999),lymph node metastasis(P=0.162),depth of invasion(P There was no statistical correlation between vascular cancer thrombus(P>0.999)and clinical TNM stage(P=0.007)of gastric cancer(P<0.05).3.Expression of SATB2 protein in gastric cancer and its relationship with clinicopathological features3.1 SATB2 protein was positively expressed in 11 cases of 100 cases of gastric cancer,the positive rate was 11%(11/100),and negative expression was found in 50 cases of non-cancer mucosa.The positive rate was 0%(0/50),compared with SATB2.The positive expressionrate of protein in gastric cancer tissues and non-cancer mucosa tissues was statistically significant(P=0.035).3.2 The expression of SATB2 protein and gender of gastric cancer patients(P=0.356),age(P=0.793),degree of differentiation(P=0.950),tumor size(P=0.442),lymph node metastasis(P=0.595),clinical TNM stage(There was no statistical correlation between P>0.999)and vascular tumor thrombus(P=0.893),but correlated with the depth of invasion of gastric cancer(P=0.026)(P<0.05).4.Correlation between expression of hMSH6,hPMS2 and SATB2 in gastric cancer There was a positive correlation between hMSH6 and hPMS2 protein expression in gastric cancer tissues.There was no significant correlation between SATB2 protein expression and hMSH6 and hPMS2 protein expression in gastric cancer tissues(P>0.05).Conclusions1.There is a loss of expression of hMSH6 and hPMS2 in gastric cancer tissues,but normal expression in non-cancer mucosa,suggesting that the loss of hMSH6 and hPMS2 protein expression is associated with the development of gastric cancer.2.Loss of hMSH6 protein expression was not associated with gender,age,depth of invasion,lymph node metastasis and TNM staging in gastric cancer patients,suggesting that the loss of hMSH6 expression may not be related to the progression of gastric cancer;the loss of hPMS2 protein expression is only related to tumor TNM staging.There is a statistical correlation,suggesting that the loss of expression of hPMS2 may be related to the progression of gastric cancer.3.The expression of SATB2 protein in gastric cancer was higher than that in non-cancer mucosa,and it was statistically correlated with the depth of tumor invasion,suggesting that the expression of SATB2 may be related to the occurrence and development of gastric cancer.4.The expression of mismatch repair protein hMSH6 and hPMS2 in gastric cancer tissues was positively correlated,suggesting that there may be synergistic effects in the development of gastric cancer.The expression of hMSH6 and hPMS2 protein in gastric cancer tissues has no significant correlation with the expression of SATB2 protein.It is suggested that both of them may participate in the development and progression of gastric cancer through different signaling pathways during the development of gastric cancer. |
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