Investigation of the Metabolism-Related Prognostic Gene SERPINE1 as a Prognostic Predictor in Colorectal Adenocarcinoma and Its Regulatory Mechanisms Underlying Immune Infiltration

Objective To explore the role of Metabolic-related Genes (MRGs), especially SERPINE1 , in the prognosis and immune infiltration of Colorectal Adenocarcinoma (COAD). Methods This study incorporated the transcriptomic data of colorectal adenocarcinoma (COAD) retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Based on 2752 metabolism-related genes, the Metabolism-Related Gene Prognostic Index (MRGRI) model was constructed and validated. For the SERPINE1 , a comprehensive analysis was performed, covering differential expression analysis, survival analysis, and nomogram construction. Meanwhile, its associations with the tumor microenvironment, immune response, and drug sensitivity were explored. In addition, single-cell analysis was used to verify the heterogeneous expression characteristics of SERPINE1 . Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to validate the expression level of this gene in COAD cells, providing data support for subsequent mechanistic research.. Results A total of 159 differentially expressed related to metabolic genes (DE-MRGs) were screened out, and 18 genes associated with prognosis were identified. Through LASSO regression, a prognostic model containing 13 genes was established. In this model, the survival rate of the high-risk group was relatively low and the risk score demonstrated strong predictive power. Furthermore, a total of 72 differential genes related to the prognosis of MRGs were obtained, among which SERPINE1 was the hub gene. In COAD tissues, high expression of SERPINE1 indicated a poor prognosis and was correlated with disease stages. The nomogram provided accurate predictions. The differentially expressed genes were mainly enriched in pathways related to immune receptor activity. SERPINE1 regulated the immune microenvironment, affected tumor immune escape and immunotherapy responses, and overexpression of it would reduce drug sensitivity.Single-cell analysis reveals heterogeneous expression of SERPINE1 in macrophages. Conclusion In the MRGs risk model, SERPINE1 is a hub gene that plays a crucial role in the prognosis, immune infiltration and drug sensitivity of COAD.