Analysis Of RAI14 With Prognosis、immune Cell Infiltration And Drug Sensitivity In Stomach Adenocarcinoma Patients

Objective: RAI14 is an F-actin regulatory protein with membrane shaping function and is highly expressed in the placenta,testis,and eye.Actin provides mechanical support to cells and provides transport pathways that exploit the cytoplasm to aid in the rapid assembly and disassembly of signaling actin networks that allow cells to migrate.Some studies have proposed that RAI14 may be the driver gene for the occurrence of some cancers.This study using bioinformatics methods,preliminarily explored the expression of RAI14 in multiple tumors,and specifically analyzed the correlation of RAI14 and immune cell infiltration in stomach adenocarcinoma(STAD).Finally,the correlation between the expression of RAI14 and drug sensitivity in STAD was predicted.Methods: In this study,the expression of RAI14 gene in different cancers were analyzed by TIMER2.0,and GEPIA software was used for supplementary analysis.The differences RAI14 protein expression levels in different cancer types were analyzed by download RAI14 protein immunohistochemical(IHC)staining images from the HPA database.The relationship between RAI14 expression and clinicopathological parameters of tumor patients were analyzed using UALCAN database,including tumor stage and degree of tumor differentiation.Using GEPIA2 "Survival Ma P" module,the correlation of RAI14 with patient OS(Overall Survival)and DFS(Disease-free Survival)were analyzed and curved.COX regression was used to analyze whether RAI14 could be an independent prognostic factor for STAD.The main mutational forms of RAI14 in Stomach adenocarcinoma were analyzed by c Bio Poral.COX regression analysis also showed that tumor metastasis status is an independent predictor of prognosis in Stomach adenocarcinoma patients,so the TIMER database ESTIMATE algorithm,CIBERSORT tool and TISIDB database were further used to study the correlation between RAI14 gene expression and the infiltration level of various immune cells in STAD.In order to study the potential mechanism of RAI14 in the occurrence and development of STAD,the GEPIA2 database was used to obtain genes that interact with RAI14,and KEGG and GO enrichment analysis were performed on these genes.Using R software GSVA package,the correlation between RAI14 expression and key EMT genes in STAD were analyzed by Spearman correlation.Finally,the correlation between RAI14 expression and drug sensitivity were predicted through R packets.Results:1.This study analyzed the expression of RAI14 in different tumor types by using the TIMER database,Suggindicated that RAI14 expressed higher levels in tumor tissues including Breast invasive carcinoma(BRCA),Head and Neck squamous cell carcinoma(HNSC),Liver hepatocellular carcinoma(LIHC),Lung adenocarcinoma(LUAD),Esophageal carcinoma(ESCA),Lung squamous cell carcinoma(LUSC),Stomach adenocarcinoma(STAD)(P<0.001),Glioblastoma multiforme(GBM)(P<0.01),Brain lower Grade Glioma(LGG),Thymoma(THYM),Diffuse large B-cell lymphoma(DLBC)(P<0.05)than the corresponding normal tissues,Suggesting that RAI14 may play as an oncogene in the aforementioned tumor types.2.In this study,the results of IHC staining of RAI14 protein provided by the HPA database were analyzed to verify that the expression of RAI14 protein in some tumor tissues such as Stomach adenocarcinoma(STAD),Lung adenocarcinoma(LUAD),Breast invasive carcinoma(BRCA),and Ovarian carcinoma(OV)tumor tissues were significantly increased compared with the corresponding normal tissues.3.In this study,the relationship between RAI14 expression and clinicopathological parameters in tumor patients were analyzed through the UALCAN database,and it was shown that RAI14 were highly expressed in patients with advanced Stomach adenocarcinoma and poorly differentiated tumors.4.The present study analyzed the correlation between RAI14 expression and the prognosis of tumor patients,and the degree of prognosis in tumors.We found that the high expression of RAI14 was significantly associated with overall survival OS and disease-free survival DFS in STAD and UVM patients,and was most significant in STAD.5.COX proportional regression analysis showed that high RAI14 expression could be used as an independent prognostic risk factor for STAD(P<0.01).6.Analysis of RAI14 genetic variant types indicates that gene amplification and gene mutations are the main types of RAI14 variation in tumors,Missense mutations are the predominant type of RAI14 mutation in STAD.7.Correlation analysis of RAI14 expression and the level of immune cell infiltration in STAD showed that high RAI14 expression was associated with higher levels of immune cell infiltration,with CD4+(R=0.251,P=7.51e-07),CD8+(R=0.329,P=5.22e-11),macrophages(R=0.606,P=2.59e-39),neutrophils(R=0.217,P=2.07e-05)and dendritic cells(R=0.234,P=4.21e-06).Moreover,the high expression of RAI14 is closely related to the macrophage polarization and immunosuppressive factors in STAD.8.By functional enrichment analysis,we found that RAI14 can activate the Rho pathway and promote epithelial mesenchymal transformation,thereby promoting the invasion and metastasis of STAD.9.The high expression of RAI14 is positively correlated with the sensitivity of drugs such as cyclopamine.Conclusion:1.RAI14 is highly expressed in most tumors,and prognosis effects in different tumors are varied,especially make sense in STAD.2.In STAD,RAI14 is closely related to immune cell infiltration,which may promote the occurrence and development of Stomach adenocarcinoma by changing the tumor microenvironment.3.Enrich of gene function further indicates that RAI14 may activate Rho pathway to promote the epithelial mesenchymal transformation process,thus promoting the invasion and migration of STAD.4.The drug sensitivity results indicate that RAI14 expression in STAD increases the sensitivity of tumor cells to anti-tumor drugs such as cyclophosphamide,providing preliminary data support for its drug selection.