Gene Expression Profiling Of Tricarboxylic Acid Cycle And One Carbon Metabolism Related Genes For Prognostic Risk Signature Of Colon Carcinoma

BackgroundColorectal cancer（CRC）is one of the most common malignant tumors in the world,and colon adenocarcinoma（COAD）is the most common pathological type of colorectal cancer.Several biomarkers associated with the survival of colorectal cancer patients have been identified.However,the predictive power of individual gene biomarkers is not sufficient.The results of the study found that various biological characteristics of tumors are closely related to metabolism,and the tricarboxylic acid cycle（TCA）and one-carbon metabolism play an important role in tumors.This study primarily identifies novel genetic signatures from the tricarboxylic acid cycle（TCA）and one-carbon metabolism to better predict COAD survival.ObjectiveTo explore the possible relationship between TCA cycle and one-carbon metabolism and prognosis,and to search for gene signatures related to TCA cycle and one-carbon metabolism to better predict the survival of COAD patients.Methods1.Using the large colon adenocarcinoma（COAD）cohort of The Cancer Genome Atlas（TCGA）database,m RNA expression profiling was performed to find the differentially expressed genes of the tricarboxylic acid cycle and the one-carbon metabolic phase pathway.2.Using univariate Cox regression analysis,multivariate Cox regression analysis and receiver operating characteristic（ROC）curve to screen the gene combination most related to the prognosis and survival of patients.3.Bioinformatics analysis of the screened genes using a variety of public databases.4.Validation of the expression of these genes in colon adenocarcinoma（COAD）tissue.Results1.There are 18 differentially expressed genes（DEGs）involved in the tricarboxylic acid cycle and one-carbon metabolism pathway between tumors and normal tissues.2.Univariate Cox regression analysis and multivariate Cox regression analysis showed that SUCLG2,SUCLG1,ACLY,SUCLG2P2,ATIC,ACO2 were associated with the survival rate of colon adenocarcinoma patients.Combined with clinical variables,the receiver operating characteristic（ROC）curve was used to screen out model 1（AUC=0.82505）,which was the most correlated variable combination model with the prognosis and survival of patients.Model 1 contains 3 genes: SUCLG2P2,SUCLG2 and ATIC.3.SUCLG2P2 and SUCLG2 were lowly expressed in colon adenocarcinoma,while ATIC was highly expressed in colon adenocarcinoma,and the expression levels of SUCLG2P2,SUCLG2 and ATIC were related to the stage of colon adenocarcinoma.Pearson analysis showed that there was a strong positive correlation between SUCLG2P2,SUCLG2 and ATIC genes in normal tissues,but there was no correlation between SUCLG2P2 and ATIC,SUCLG2 and ATIC in tumor tissues.4.The expression levels of SUCLG2P2,SUCLG2 and ATIC genes in colon adenocarcinoma tissue samples were consistent with the results of public database analysis.ConclusionsIn conclusion,the expressions of SUCLG2P2,SUCLG2 and ATIC in colon cancer and normal tissues were diff erent,and they were related to survival.The model constructed by these three genes and clinical data has a good predictive ability for predicting the survival of patients.The results suggest that SUCLG2P2,SUCLG2 and ATIC may be biomarkers or therapeutic targets for COAD.