CAD Drives Colorectal Cancer Progression through the JAK2/STAT1 Pathway and Correlates with Poor Prognosis

Background Colorectal cancer (CRC) is a highly prevalent and lethal malignant tumor that is tightly linked to metabolic reprogramming. Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) are enzymes involved in purine de novo synthesis that are overexpressed in a variety of tumors. However, the precise role and immunological regulation mechanism of CAD in CRC remain unknown. This study seeks to investigate the expression, function, and clinical importance of CAD in CRC. Methods The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and 121 CRC patients from Guangxi Medical University Cancer Hospital were included in research. We analyzed datasets through bioinformatics covered clinical pathological features, prognosis model, gene regulation, immune infiltration, and drug sensitivity. Experimental assessments further illustrated how CAD promote CRC malignancy and its possible function. Results Based on above evidence, we found the levels of mRNA and protein for CAD were significantly elevated in CRC tissues and were independently linked to a poor prognosis. Also, CAD can be a trigger that enhances the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1 (STAT1), leading to CRC progression. Bioinformatic analysis depicted a map related to immunosuppressive microenvironment and weak response to immunotherapy when CAD highly expressing. Conclusions CAD may act as a prognostic biomarker and a therapeutic target for CRC, presenting a novel insight for combined treatment strategies.