Huang Pin, Guo Ke, Tu Jiancheng, Fang Jian, Zhou Liang, Luo Xiagang, Xu Hubin
Department of General Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Hum Mutat. 2025 Aug 6;2025:6705599. doi: 10.1155/humu/6705599. eCollection 2025.
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.
结直肠癌（CRC）是全球癌症相关发病和死亡的主要原因。尽管基于奥沙利铂的化疗（CT）在CRC治疗中具有疗效，但CT耐药仍然是患者获得成功治疗结果的主要障碍。上皮-间质转化（EMT）是癌症转移中的关键细胞过程，在对CT的耐药中起关键作用。肿瘤微环境（TME），特别是癌症相关成纤维细胞（CAF），已知会促进EMT和治疗耐药。在此，我们采用单细胞RNA测序（scRNA-seq）来分析接受CT和非化疗（nCT）治疗的患者的原发性CRC肿瘤样本。我们的研究确定了对奥沙利铂耐药的特定上皮细胞簇，阐明了参与EMT和耐药的分子途径。此外，我们探讨了CAF亚群在TME中促进耐药的作用。我们的研究结果强调了功能免疫分析和基因组分析在识别预测CT反应的潜在生物标志物以及改进个性化治疗策略方面的重要性。这项工作为CRC中奥沙利铂耐药的分子机制提供了新的见解，并支持开发基于免疫的新型治疗方法以改善患者治疗结果。
