Expression Of KIRREL In Gastric Cancer Is Correlating With Prognosis And Immune Infiltration

objective:Kin of IRRE protein 1(KIRREL),also known as NEPH1,is a member of cell adhension molecule immunoglobulin superfamily.The main component of KIRREL are transmembrane domain,extracellular domain and intracellular domain.Firstly,overexpression of KIRREL is discovered in podocytes and affected glomerular permeability by interacting with Nephbrin.Then,there are many studies reveal that expression of KIRREL plays a essential role in neuronal development,myocyte repair and tumorigenesis and progression.However,the mechanism of KIRREL related to the occurrence of gastric cancer is still unclear.In this study,the relationships between KIRREL expression and prognosis,clinicopathological parameters,biological function and immune cell infiltration in gastric cancer was investigated with bioinformatics,and analyze its possible mechanism in the occurrence,invasion and metastasis of gastric cancer.This suggests that KIRREL is a new prognostic biomarker and target for immunotherapy in gastric cancer.Methods :(1)The expression of KIRREL in pan-cancer,including gastric cancer,was analyzed by TIMER database.We used UALCAN database to explore the connection between the expression of KIRREL and the clinicopathological parameters,such as tumor grade,cancer stages,gender and nodal metastasis status。(2)The prognostic value analysis were investigated using Sanger Box,GEPIA and Kaplan-Meier database.(3)The co-expression genes were filtered out using GEPIA and STRING database.Sanger Box database were used to conduct Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.(4)TIMER and Sanger Box database were used to evaluate the correlation between KIRREL and the immune cell infiltration,immune checkpoint genes and ESTIMATE score.The relationship between expression levels of KIRREL and immune cell-specific marker infiltration were investigated using GEPIA database.Results:(1)KIRREL expression was higher in most human cancers than in paired tissue,especially in gastric cancer.(2)There have strong relationships between the expression of KIRREL and individual cancer stage,tumor grade and patients’ age,among other clinicopathological parameters.(3)High expression of KIRREL is associated with poor prognosis in cancer patients.(4)149 co-expression genes of KIRREL were researched using GEPIA and STRING database,and found that they were mainly enriched in cell migration,biological adhesion and circulatory system development,among other pathway.By screening the co-expression genes data of KIRREL,We found that The expression of ANTXR1 is significantly positively correlated with KIRREL,and had higher expression in gastric cancer.It is related to the poor prognosis of gastric cancer patients.It is a potential binding protein of KIRREL,and may participate in the occurrence,invasion and metastasis of gastric cancer.The expression of KIRREL is positively correlated with the infiltration level of immune cells,specific markers and immune checkpoint genes in the tumor microenvironment(P<0.05),had no significant correlation with B cells(P>0.05).The infiltration levels of Macrophage is associated with poor prognosis in patients with gastric cancer.The copy number variation of KIRREL had a strong influence with infiltration level of immune cells.The expression of KIRREL was significantly positively correlated with the scores of ESTIMATE,normal and immune.Conclusion:KIRREL may promote the progress of gastric cancer by regulating immune infiltration in tumor microenvironment,and it may serve as a vital potential prognosis and immunological gastric cancer biomarker.Moreover,KIRREL could be a new target for immunotherapy in gastric cancer.