| Objective: This study from the angles of computational biology and clinical gastric cancer samples analysis of HER2 levels in gastric cancer tissue immune to tumor invasion and the influence of the tumor progression and the clinical significance of the systemic inflammatory response,explore the positive expression of HER2 in gastric cancer tissue in the body presence of inhibition in the antitumor immune response,and give play to the role of immunosuppression potential mechanism.Materials and methods :(1)To retrieve The Cancer Genome Atlas(TCGA)database and download transcriptome rna-seq gene sequencing and proteomic expression data in gastric Cancer tissues.After the standardized processing of the data,the degree of infiltration of 22 immune cells in gastric cancer tumor tissues was calculated based on CIBERSORT software using the wholeprotein-encoded genomic expression profile data of gastric cancer.R project was used to analyze the clinical significance of 22 kinds of immune cells’ degree of infiltration in gastric cancer tissues on the occurrence,progression and prognosis of tumor.Meanwhile,kaplan-meier method was used to calculate the prognostic value of HER2 protein expression in gastric cancer tissues,and the relationship between HER2 protein and immune cell infiltration was analyzed to determine the clinical significance of HER2 protein expression in gastric cancer and its effect on tumor immunity in gastric cancer.(2)a total of 237 clinical tissue samples of gastric cancer were included,and the HER2 protein status was detected by immunohistochemistry(IHC)and Fluorescence in situ hybridization(FISH)techniques.Data of clinical and pathological features,blood routine,c-reactive protein(CRP),hypersensitive c-reactive protein(hs-crp)and CA199 of all included cases were collected.The relationship between HER2 protein and clinicopathological characteristics and systemic inflammatory response indicators was analyzed by the chi-square test.Based on the improved Glasgow score of tumor prognosis of systemic inflammation,the value of HER2 protein status in gastric cancer tissues in systemic inflammatory response and prognosis of gastric cancer patients was evaluated.Results:(1)Infiltration and significance of immune cells in gastric cancer tissues: the calculated results showed that plasma cells,CD8+ T cells,CD4+ T cells and macrophages including M0,M1 and M2 all showed relatively obvious infiltration in gastric cancer tissues,and there were significant differences between cancerous tissues and non-cancerous tissues(P<0.05).Among them,m1-type macrophages(M1:0.0736±0.0443 vs 0.0242±0.0100)and m2-type macrophages(M2: The infiltration rate of 0.1182±0.0616 vs 0.0641±0.0262 and CD4+ T cells(0.0482±0.056 vs 0.0076±0.0106)was higher in gastric cancer tissues,while that of plasma cells(0.0557±0.0612 vs 0.3136±0.0714)and CD8+T cells(0.1206±0.0932 vs 0.1412±0.0528)was opposite.With the progression of tumor T stage,the infiltration degree of natural killer Cells(NK Cells),Mast Cells activated,Eosinophils,Neutrophils and other immune Cells decreased significantly,while the infiltration degree of m1-type macrophages increased with the progression of T stage(P<0.05).The infiltration of CD8+ T lymphocytes may influence the lymph node metastasis of gastric cancer to a certain extent(P=0.014).In addition,plasma cells,regulatory T cells(Tregs),mononuclear cells(Monocytes),and mast cells infiltration were significantly different in different age groups(P<0.05).Prognosis and uni-factor Cox regre-ssion analysis suggested that CD4+ memory T cells and neutrophils could be used as independent factors to affect the prognosis and survival of gastric cancer patients(P<0.05),while CD8+ T lymphocytes had certain potential in the evaluation of the prognosis of gastric cancer patients(P=0.0847).(4)based on TCGA survival data analysis,there was no statistically significant difference between the prognosis of HER2 protein and gastric cancer for the time being,but in the statistical analysis of pathological M stages,it was found that the increased level of HER2 protein was associated with a greater probability of metastasis of gastric cancer(0.6428±1.2762 vs 0.0559±0.987,P=0.01).The results of correlation analysis showed that the level of HER2 protein in gastric cancer samples was negatively correlated with CD4+ T memory cells and CD8+ T cells activated by gastric cancer prognostic protective factor(r<0),and positively correlated with prognostic risk factor m2-type macrophages(r>0).These results suggested that with the increase of HER2 protein in gastric cancer tissues,tumor invasive killer immune cells decreased,while immune cells that assisted tumor immune escape and promoted tumor progression increased.(2)the relationship between HER2 status and pathological characteristics and inflammatory indicators in clinical cases:(1)in clinical samples of gastric cancer,a total of 67cases(28.27%)were amplified with positive HER2 including IHC results(3+)and FISH detection.HER2 negative results included IHC results 0～1+ and FISH test interpretation of no amplification in a total of 170 cases(71.73%).In patients with positive HER2,the incidence of vascular infiltration of tumor cells increased significantly(50.8% vs 35.3%,P=0.032)and was closely related to the pathological T stage and histological differentiation degree of gastric cancer(P<0.001).In the tumor-bearing state,the abnormal increase rate of circulating c-reactive protein and hypersensitive c-reactive protein was more significant in her2-positive patients(29.3% vs 12.9%,P=0.017).62.8% vs 36.2%,P=0.003),and the prognostic risk of NLR,PLR and PI also increased,which may indicate that positive HER2 is associated with poor prognosis in patients with gastric cancer.Conclusion: The infiltrated CD4+ T cells and CD8+ T in gastric cancer tissues play a role as the main anti-tumor immune cells.Positive HER2 may inhibit the activation of anti-tumor immune cells and be correlated with the activation of systemic inflammatory response.Therefore,inhibiting the expression of HER2 and activating the body’s anti-tumor immunity may be a new direction in the immunotherapy of gastric cancer. |
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