Abstract
BACKGROUND: The aim of this study was to clarify the expression of gamma-aminobutyric acid type A receptor delta subunit (GABRD) gene in pan-cancer and its correlation with patient prognosis, and to investigate the function and possible mechanism of GABRD in colorectal cancer (CRC). METHODS: The Cancer Genome Atlas (TCGA) data were used to analyze the expression differences of GABRD in pan-cancer, and the correlation between GABRD and clinical prognosis of various tumors was analyzed by Cox regression method. According to the expression level of GABRD, Gene Function Annotation (GO) and Kyoto Encyclopedia of Genomes (KEGG) functional enrichment analysis were performed on the differentially expressed genes. Expression of GABRD gene and 44 marker genes of three types of RNA modification (m1A (10), m5C (13), m6A (21)) genes in different tumors was observed. Pearson correlation of GABRD gene and marker genes of five immune pathways was measured. RESULTS: : TCGA data analysis showed that GABRD was significantly upregulated in various tumor tissues, especially COAD and READCOAD. Survival analysis showed that GABRD was a prognostic protective factor in CRC (p < 0.001). The results of survival nomogram showed that GABRD, age, and tumor (T) lymph node (N) distant metastasis (M) stage were independent prognostic factors, and the survival model C-index was 0.724 (0.644-1). Gene enrichment and functional analysis showed that GABRD may be related to protein digestion and absorption, ECM-receptor interaction, extracellular structure organization, extracellular matrix organization, pancreatic secretion, and antimicrobial humoral response. The expression of GABRD was positively correlated in m1A-, m5C-, and m6A-related genes. The GABRD gene was found in B cell, T cell CD4, T cell CD8, neutrophil, macrophage in TCGA-COAD (N = 282), and TCGA-COADREAD (N = 373). The infiltration level and DC was significantly positively correlated (p < 0.05). Also, the Pearson correlation coefficient is the largest. CONCLUSION: The involvement of GABRD in the occurrence and development of CRC may be related to protein digestion and absorption, ECM-receptor interaction, extracellular structure organization, extracellular matrix organization, pancreatic secretion, and antimicrobial humoral response. GABRD can be used as a molecular marker for the prognosis of CRC.