POC1A Acts As A Promising Prognostic Biomarker Associated With Immune Cell Infiltration In Gastric Cancer

Background: As one of the most common malignant tumors,gastric cancer has a high mortality rate worldwide,whose prognosis is impacted by the tumor microenvironment(TME)mediated immune infiltration.As a key protein on the centrosome,POC1 centrin A(POC1A)plays an important role in the regulation of centrioles,however,which even has no relevant research in gastric cancer.Therefore,it is significant to ensure the relationship among POC1A,gastric cancer immune infiltration and prognosis,which guides the diagnosis and treatment of early gastric cancer.Purpose: 1.To explore the expression of POC1A in gastric cancer and verify the impact of POC1A on the prognosis of gastric cancer patients.2.To verify the correlation between POC1A and the clinicopathological characteristics of gastric cancer.3.To investigate the relationship between POC1A and the tumor microenvironment(TME)in gastric cancer.4.To study the correlation between POC1A and immunocyte infiltration in gastric cancer.5.To study the influence of POC1A and immunocyte infiltration towards the clinical prognosis of gastric cancer.Methods: 1.Predicting the POC1A expression in gastric cancer and its correlation with the prognosis of gastric cancer patients through public databases such as TCGA and GEO.2.Verifying the m RNA and protein expression of POC1A in gastric cancer and adjacent tissues by real-time fluorescent quantitative PCR(q RTPCR)and immunohistochemistry(IHC).3.Analyzing whether POC1A m RNA and protein expression is correlated with clinical characteristics including clinical stage,tumor location and tumor size by statistical methods.4.Analyzing gene expression data in public databases through ESTIMATE algorithm,single sample GSEA(ss GSEA)analysis and CIBERSORT deconvolution algorithm,which analyzed with result of TIMER database together to predict the relationship among POC1A,tumor microenvironment(TME)and immunocyte infiltration.5.Not only acquiring the expression of POC1A and M2 tumor-associated macrophage-specific marker in gastric cancer tissue by immunohistochemistry(IHC)but also investigating their correlation and their influence on the prognosis of gastric cancer patients via statistical analysis.Results: In this study,we predict that POC1A act as a tumor suppressor effect in gastric cancer by analyzing TCGA and GEO public databases,and verify it through tissue samples and corresponding clinical prognostic in our center for verification,we found that the m RNA and protein expression of POC1A in gastric cancer tissues were significantly lower than adjacent normal tissues(P<0.001),and KM survival analysis showed that the high expression of POC1A had significant negative correlation with the poor prognosis of gastric cancer(P<0.05).At the same time,POC1A is not only correlated with N stage in several clinicopathological factors(P<0.05),but also can be regarded as an independent prognostic factor(HR: 0.56,95%CI: 0.33-0.96,P=0.034)to exert a tumor suppressor effect.Therefore,a variety of bioinformatics analysis methods and multiple public databases were used to analyze the relationship among POC1A,tumor microenvironment and immune infiltration,which demonstrated that POC1A significantly had negative correlation with tumor microenvironment and immune infiltration(R<0,P< 0.001).In addition,the results of bioinformatics and immunohistochemistry revealed that the high immune infiltration of M2 tumorassociated macrophages(TAM)in gastric cancer,which significantly had negative correlation with the high POC1A expression(P<0.05),can induce the poor prognosis of gastric cancer(P<0.001).Furthermore,survival analysis showed that patients with gastric cancer who only expressed POC1A had a better prognosis than patients with CD163(P<0.001),a specific marker of M2 tumor-associated macrophages,expression only.Besides,the comprehensive expression of POC1A and CD163 can be regarded as an independent prognostic factor to affect the overall survival of gastric cancer patients(P=0.034).Conclusion: In gastric cancer,POC1A can role as an independent prognostic factor to mediate the better prognosis,whose expression is negatively correlated with the M2 tumor-related macrophage immune infiltration,which act as a tumor promoter.The complex of the two factors can be used as an independent prognostic factor,which affects the prognosis of gastric cancer patients with tumor volume together.Therefore,we hold the view that POC1A can be regarded as a new prognostic biomarker related to the immune infiltration of M2 tumor-associated macrophages.