The Expression Of BEST4 Protein And Its Correlations With HER2,Ki-67 And Mismatch Repair Protein In Colon Cancer

Objective:(1)The meaning of BEST4 protein in colon cancer(CC)and adjacent normal mucosa tissues was detected,and the correlation between the expression of BEST4 protein and the clinicopathological factors of patients was analyzed.(2)The expressions of HER2,Ki-67 and MMR gene proteins in colon cancer tissues were detected,and the correlations with HER2,Ki-67 and MMR gene proteins in colon cancer tissues were analyzed.(3)Application of bioinformational methods to screen the significant genes related with BEST4,KEGG pathway enrichment analysis and the gene ontology annotation of genes with significant difference were conducted,and the biological functions of BEST4 was predicted.Methods:(1)199 cases of human CC samples were collected from First Affiliated Hospital of Soochow University.The expression of BEST4 and the correlations between BEST4 expression and clinicopathological factors were measured using immunohistochemistry.(2)IHC was used to detect the expression of HER2,Ki-67,DNA mismatch repair(MMR)gene proteins MLH1,MSH2,MSH6 and PMS2 in the CC tissues,and to analyze the correlations among BEST4,HER2,Ki-67,and DNA mismatch repair(MMR)gene protein expression in colon cancer.SPSS20.0 software was used for statistical analysis.(3)Bioinformatics analysis using R language software and bioinformatics tools.Results:(1)BEST4 expression levels were substantially upregulated in the primary CC tumors compared with matched surrounding tissues(1±1.86)(P=0.001),moreover,a strong association between tumor-node-metastasis(TNM)stage and increased BEST4 expression in CC(P=0.010),in addition,the results showed that the high expression of BEST4 protein correlates with tumor site,Tumors with the higher BEST4 expression were more likely to occur in the right colon,but those tumors with low BEST4 expression were more likely to occurin the left colon(P=0.032).There was also a correlation between BEST4 protein expression and lymph node metastasis.(2)The expression of BEST4 protein was positively correlated with HER2 protein(P=0.05,r=0.139).BEST4 protein showed a negative correlation with microsatellite instability(MSI)indicated by mismatched repair protein(P=0.011,r=-0.180).There was a negative correlation between the expression of BEST4 protein and Ki-67 protein,but the difference was not statistically significant(P=0.228,r=-0.086).(3)Bioinformatics results showed that BEST4 gene is closely related with biological functions such as ion transport,synthesis of steroid hormones,drug metabolism and retinol metabolism.Conclusion:(1)BEST4 protein is associated with tumor location,tumor progression,lymph node metastasis and other prognostic factors in colon cancer.(2)BEST4 has synergistic effects with HER2 and mismatched repair proteins in the development of colon cancer.(3)Bioinformatics results suggest that BEST4 gene may be involved in drug metabolism,suggesting a new target for the treatment of colon cancer.