Serum miR-424-3p is a promising prognostic biomarker for colorectal cancer by targeting Gasdermin E

Colorectal cancer (CRC) has a poor prognosis, highlighting the urgent need for reliable prognostic biomarkers. Given the stability of microRNAs (miRNAs) in serum, this study aimed to identify and validate a serum miRNA as a robust biomarker for CRC prognosis. Serum and tissue samples were collected from CRC patients in a discovery cohort ( n = 80) and an independent validation cohort ( n = 64). Candidate miRNA expression was quantified by quantitative reverse transcription polymerase chain reaction. Prognostic performance was evaluated using receiver operating characteristic curve analysis, and progression-free survival (PFS) was assessed by Kaplan-Meier analysis. Multivariate Cox regression identified independent risk factors for PFS. Integrative bioinformatics predicted target genes, followed by cellular assays, including assessments of cell viability, migration, invasion, and pyroptosis. Serum miR-424-3p levels were elevated in CRC patients with poor prognosis. High miR-424-3p expression correlated with adverse clinicopathological features, including depth of invasion ≥ 1/2, TNM stage Ⅲ, lymph node metastasis, and poor differentiation, and was identified as an independent risk factor affecting PFS. Patients with higher miR-424-3p levels exhibited a significantly shorter 3-year PFS rate. Mechanistically, miR-424-3p may promote CRC malignancy by directly targeting Gasdermin E (GSDME), thereby suppressing GSDME-mediated mitochondrial dysfunction and pyroptosis. Furthermore, a prediction model combining miR-424-3p with carcinoembryonic antigen (CEA) and carbohydrate antigen 19 − 9 (CA199) yielded excellent prognostic accuracy. Serum miR-424-3p serves as an independent prognostic predictor in CRC, mechanistically linked to the suppression of GSDME-mediated pyroptosis. The multi-marker panel represents a promising non-invasive tool for enhanced prognostic stratification in CRC patients.