Upregulated AGMAT is Associated with Prognosis in Colorectal Cancer

Abstract

Background: Agmatinase (AGMAT) has been specifically reported to be highly expressed in several malignancies. Therefore, this study aims to investigate the role of AGMAT in colorectal cancer (CRC) and assess its potential as a prognostic biomarker. Methods: We used The Cancer Genome Atlas (TCGA) database to identify differentially expressed genes in CRC compared to the healthy controls. Subsequently, we performed enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases to gain insights into the biological processes and cellular signaling pathways influenced by these differentially expressed genes (DEGs). The most informative prognostic genes among these DEGs were predicted by combining Least Absolute Shrinkage and Selection Operator (LASSO) regression and best subset selection, ultimately identifying the eight most relevant genes. Furthermore, we developed gene-based risk scores using Cox coefficients for these eight prognostic genes. The prognostic ability of the risk score was evaluated using two methods: time-dependent receiver operating characteristic (ROC) analysis and Kaplan-Meier (KM) survival analysis. Additionally, the correlation between AGMAT expression and prognosis in CRC tissues was investigated utilizing GEPIA 2 and the Human Protein Atlas (HPA) database. Finally, we employed RT-qPCR to quantify AGMAT mRNA expression levels in CRC tissues samples. Results: Our analysis of TCGA data revealed 1917 DEGs, including 928 upregulated and 989 downregulated genes. Among them, 8 genes, including Matrix Metallopeptidase 1 (MMP1), Serine Protease Inhibitor Kazal-Type 1 (SPINK1), Cluster of Differentiation 24 (CD24), Serine Protease Inhibitor Kazal-Type 4 (SPINK4), AGMAT, EPH Receptor B2 (EPHB2), C2 Calcium-Dependent Domain Containing 4A (C2CD4A), Pituitary Tumor-Transforming Gene 1 (PTTG1), were significantly associated with prognosis in CRC. Furthermore, we observed upregulated AGMAT expression in CRC tissues. Additionally, we found a significant association between elevated AGMAT expression and decreased overall survival (OS) and disease-free survival (DFS) in patients with CRC (p-value < 0.05). Conclusions: This study demonstrates that AGMAT is highly expressed in CRC tissues and is significantly associated with poorer prognosis in CRC patients. These findings suggest that AGMAT expression could serve as a biomarker for predicting survival in CRC, potentially offering new insights into its role in CRC development and paving the way for future treatment options.