Based On The Three Immune Genes INHBA,JAG2 And CCL19 To Establish A Relevant Immune Risk Score Model To Predict The Prognosis Of Colon Cancer Patients

Objective: Colorectal cancer(CRC)is the leading cause of cancer deaths and most common malignant tumors worldwide.Immune-related genes(IRGs)can predict prognoses of patients and the effects of immunotherapy.A series of colon cancer(CCa)samples from The Cancer Genome Atlas(TCGA)were analyzed to provide a new perspective into this field..Methods: Differential IRGs and IRGs with significant clinical outcomes(s IRGs)were calculated by the limma algorithm and univariate COX regression analysis.The potential molecular mechanisms of IRGs were detected by PPI,KEGG and GO analysis.Immune-related risk score model(IRRSM)was established based on multivariate COX regression analysis.Based on the median risk score of IRRSM,the high-risk group and low-risk group were distinguished.The expression levels of IHNBA and JAG2 and relationships between IHNBA and clinical features were verified by RT-q PCR.Colon cancer(CCa)tissues and adjacent normal tissues were collected from 56 patients admitted to The Second Affiliated Hospital of Chongqing Medical University and diagnosed with CCa.Human colonic epithelial cell line(NCM460)and CCa cell lines(CACO-2,HT29,SW480 and HCT116)were purchased from the American Type Culture Collection(Manassas,Virginia,USA).Cells were cultured in 1640 and DMEM supplemented with 10% fetal bovine serum(FBS),100 U/ml penicillin and 100 mg/ml streptomycin(Gibco,Gaithersburg,MD,USA).Cells were incubated at 37°C in 5% CO2.Results: A series of transcriptome RNA-sequencing data of 39 normal colon samples and 398 CCa samples were downloaded from the TCGA data portal.Based on limma algorithm,we screened 1550 differentially expressed CCa genes,of which 667 were down-regulated and883 were up-regulated.Next,the 20 most up-regulated and down-regulated genes were respectively confirmed by the values of log2∣FC∣.From the immune system process and immune response of Molecular Signatures Database,we further identified 331 IRGs,of which 29 genes including 12down-regulated and 17 up-regulated IRGs were recognized to be associated with CCa through the correlation analysi(CXCL8,CXCL12,SAA1,CCL20,CCL5,CCL19,MMP9,CXCL13,CCL21 and CCL24 were identified).we employed univariate COX regression analysis and identified6 s IRGs,such as CXCL12,INHBA,RUNX1,JAG2,CCL19 and IFITM2.In order to establish the IRRSM,we selected the 3 s IRGs(INHBA,JAG2 and CCL19)among the 6 s IRGs using multivariate COX regression analysis.We found the expression levels of INHBA were enhanced in the advanced T-stages;the expression levels of INHBA and JAG2 decreased in the early N-stages;the expression levels of JAG2 were evaluated in advanced M-stages.the IRRSM could be regarded as an independent prognostic factor.we established a nomogram of CCa patients utilizing multivariate COX analysis of 3 s IRGs in the IRRSM.Conclusion: In the present manuscript,we analyzed the roles of s IRGs in predicting and evaluating the clinical prognoses of CCa patients and verified the predictive value of some s IRGs.Our results provide a new perspective for immunotherapies and establish a reliable and accurate IRRSM to predict the prognoses of CCa patients.