Abstract / Summary
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Despite advances in multiple treatment modalities, resistance, recurrence, and poor outcomes remain major challenges, particularly in advanced disease. Therefore, novel prognostic biomarkers and candidate molecular targets are urgently needed. In this study, candidate genes were identified through integrative screening of the TCGA database and metabolism-related gene sets, followed by multicenter validation using multiple GEO cohorts. Syntaxin 1A (STX1A) was subsequently recognized as a candidate gene with significant prognostic value. Enrichment analysis was performed to explore STX1A-associated biological pathways. In addition, CIBERSORT and TIDE algorithms were applied to evaluate the relationship between STX1A expression, immune cell infiltration, and immunotherapy response. Finally, siRNA-mediated knockdown experiments, together with CCK-8, colony formation, wound healing, and Transwell assays, were conducted to validate its biological functions. STX1A was significantly upregulated in CRC tissues across the TCGA cohort and multiple independent GEO datasets. In the TCGA cohort, high STX1A expression remained significantly associated with unfavorable overall survival after multivariable adjustment. Functional enrichment analyses further revealed that STX1A expression was closely associated with activation of the calcium signaling pathway, cAMP signaling pathway, glycerophospholipid metabolism, and inositol phosphate metabolism. Moreover, high STX1A expression was significantly correlated with increased M2 macrophage infiltration, elevated expression of immune checkpoint molecules, and higher TIDE scores. Functional experiments demonstrated that STX1A knockdown markedly inhibited the proliferation, migration, and invasion of CRC cells while promoting apoptosis. STX1A is significantly upregulated in CRC tissues and is associated with unfavorable prognosis, immune microenvironment characteristics, and malignant cellular phenotypes. These findings suggest that STX1A may serve as a potential prognostic biomarker for CRC and provide a basis for further investigation of its biological role in CRC. However, the current evidence is primarily derived from transcriptomic analyses and in vitro experiments, and in vivo validation is still lacking. Further validation using animal models and independent clinical cohorts is therefore warranted.