Comprehensive analysis of the critical role of the epithelial mesenchymal transition subtype - TAGLN-positive fibroblasts in colorectal cancer progression and immunosuppression.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in tumor metastasis and immune suppression in colorectal cancer (CRC). However, the specific mechanisms of EMT and its relationship with the clinical prognosis and immunotherapy response in CRC patients remain unclear. In this study, we identified TAGLN-positive fibroblasts (TAGLN⁺Fib) as a cancer-associated fibroblast (CAF) subtype within the tumor microenvironment (TME) that promotes tumor metastasis and immune evasion. High EMT scores, strongly associated with TAGLN expression, were correlated with advanced tumor stages, poor prognosis, and resistance to immunotherapy. Functional experiments demonstrated that TAGLN knockdown significantly reduced CRC cell proliferation, migration, and EMT phenotypes in vitro and suppressed tumor growth in vivo. Furthermore, TAGLN⁺Fib closely interacted with MMP7-positive tumor epithelial cells and SPP1-positive macrophages, forming a pro-metastatic and immunosuppressive network. An EMT-TME risk model constructed using TAGLN⁺Fib exhibited robust predictive power for CRC prognosis and immunotherapy response. This study reveals the association of EMT scores with CRC prognosis and immunotherapy response, highlights TAGLN⁺Fib's critical role in tumor progression, and develops an EMT-TME risk model, offering insights for personalized CRC treatment and precision medicine.