The Expression Of CENPM In Liver Cancer And Its Relationship With Clinical Parameters And Tumor Infiltrating Lymphocytes:a Study Based On Bioinformatics Analysis

Aim:To explore the potential diagnostic,treatment and prognostic value of Centromere protein M(CENPM)in patients with Hepatocellular carcinoma(HCC).Methods:First,the mRNA Expression of CENPM in HCC and normal tissues were investigated in the public databases of Oncomine and GEPIA.GEPIA and Kaplan Meier plotter databases were used to investigate the tumor pathological stages and survival data of patients with differential expression of CENPM,and Cbioportal database was used to investigate the mutation of CENPM.The correlation between the CENPM mRNA and 28 types of tumor-infiltrating lymphocytes(TILs)were further analyzed by TISIDB database.Immunohistochemical staining was performed on the HCC and adjacent normal tissues from 20 patients diagnosed with HCC to verify the expression of CENPM.Results:We found that the CENPM mRNA level in HCC was significantly higher than those in normal tissues.The Fold Change(FC)were ranged from 2.173 to 3.651,and upregulated CENPM were significantly correlated with tumor stages in HCC patients(p<0.001).The results of Cbioportal showed a very low mutation rate of CENPM(mutation rate<0.1%,1/1487 patients).The results from the Kaplan Meier Plotter database showed that patients with higher CENPM mRNA expression had significantly poorer overall survival(OS),progression-free survival(PFS),relapse-free survival(RFS),and disease-specific survival(DSS).Furthermore,higher levels of CENPM mRNA were associated with worse OS in men who did not consume alcohol and were not infected with hepatitis virus.The TISIDB database showed that the top 5 lymphocytes were positively correlated with the expression of CENPM,which were activated CD4+T cells(Rho=0.484,p=2.2e-16),γδT cells(Rho=0.146,p=0.00487),CD56dim natural killer cells(Rho=0.141,p=0.00633),Th2 cells(Rho=0.121,p=0.0191)and activated CD8+T cells(Rho=0.105,p=0.0426),respectively.The top 5 lymphocytes that were negatively correlated with the expression of CENPM were eosinophilic(Rho=-0.357,p=1.74E-12),Th1 cells(Rho=-0.238,p=3.65E-06),immature dendritic cells(Rho=-0.194,p=0.000173),plasmacytoid dendritic cells(Rho=-0.188,p=0.000271)and natural killer cells(Rho=-0.18,p=0.000475).Immunohistochemical staining showed that CENPM was overexpressed in 80%(16/20)of HCC patients.Conclusion:CENPM mRNA and protein are overexpressed in HCC tissues,and the overexpression of CENPM is closely related to the abundance of various tumorinfiltrating lymphocytes,and is significantly related to tumor stages and poorer prognosis of patients.These results suggest that CENPM may be a potential prognostic and therapeutic biomarker for HCC patients.