Analysis of metabolic associated gene DLAT expression in colorectal cancer based on multi-database and its clinical significance / 解放军医学杂志

ABSTRACT

Objective To screen the metabolic associated genes (MAG) that are related to the survival of colorectal cancer (CRC) patients, investigate the relationship between the expression of dihydrolipoamide S-acetyltransferase (DLAT) and clinical significance and prognosis value in CRC, and establish the DLAT co-expression molecular regulatory network. Methods The cancer genome atlas (TCGA) database combined with whole genome transcript sequencing data and clinical case data were used to do the survival analysis of candidate MAG; The DLAT expression in CRC and the relationship between the expression level and pathological characteristics and prognosis of CRC patients were analyzed through GEO database, Oncomine and KM-plotter platforms. The DLAT co-expression gene lists were searched in cBioPortal and STRING to analyze functional clustering and pathway enrichment, and establish the DLAT co-expression molecular regulatory network. Results Survival analysis in multiple databases indicated that DLAT was the most relevant gene in candidate MAGs for survival in CRC patients (P0.05). Functional clustering of DLAT co-expression genes showed that DLAT was involved in the biological process including mitotic cell cycle, prolong and termination of mitochondrial protein translation, none-coding RNA metabolism and DNA conformation change. Pathway enrichment revealed that DLAT participated in the pathways including tricarboxylic acid cycle, oxidative phosphorylation and pyruvate metabolism. DLAT co-expression molecular regulatory network was established and 10 nodes with the highest connectivity were obtained as follows PAICS, MAD2L1, HSPD1, GART, CS, RRM1, MRPL3, BUB1, CCNB1 and CHEK1. Conclusions The expression of metabolic gene DLAT in colorectal cancer is high, but the expression is lower in advanced colorectal cancer than in early colorectal cancer, and the prognosis is poor in patients with low expression, the TNM stage is late, and lymph node metastasis is more likely to occur in patients with advanced colorectal cancer. This finding lays a foundation for the research and application of potential molecular markers related to metabolism in colorectal cancer.