Single‐Cell RNA Sequencing Reveals LEF1 as a Prognostic Biomarker for Poor Outcomes in Oxaliplatin‐Resistant Colorectal Cancer

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Despite the efficacy of oxaliplatin-based chemotherapy (CT) in CRC treatment, CT resistance remains a major obstacle to successful patient outcomes. Epithelial-mesenchymal transition (EMT), a key cellular process in cancer metastasis, plays a pivotal role in resistance to CT. The tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), is known to contribute to EMT and therapy resistance. Here, we employ single-cell RNA sequencing (scRNA-seq) to analyze primary CRC tumor samples from patients undergoing CT and nonchemotherapy (nCT) treatments. Our study identifies specific epithelial cell clusters resistant to oxaliplatin, elucidating the molecular pathways involved in EMT and resistance. Furthermore, we explore the role of CAF subpopulations in promoting resistance within the TME. Our findings highlight the importance of functional immune profiling and genomic analyses in identifying potential biomarkers for predicting CT responses and improving personalized treatment strategies. This work provides new insights into the molecular mechanisms of oxaliplatin resistance in CRC and supports the development of novel immune-based therapeutic approaches to enhance patient outcomes.