Association between cancer-associated fibroblasts and prognosis of neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma: a bioinformatics analysis based on single-cell RNA sequencing.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent and aggressive subtype of esophageal cancer, posing a significant mortality and economic burden, especially in East and Southeast Asia. Current therapeutic strategies have limitations in improving patient survival, particularly regarding disease progression and resistance. This study aimed to investigate the impact of neoadjuvant chemoradiotherapy (NCRT) on the ESCC microenvironment. METHODS: We utilized single-cell RNA sequencing to systematically characterize the tumor and cancer-associated fibroblasts (CAFs) subtypes. Marker genes of myofibroblastic CAFs (myCAFs) were employed to establish a prognostic model and verify its application in other datasets. Other experiments were conducted on clinical samples to explore potential ESCC risk-related genes. RESULTS: Our bioinformatics and statistical analyses revealed an increased proportion of fibroblasts and epithelial cells in NCRT and identified the Ep_c1 subtype associated with a better prognosis. Further results indicated a complex communication network between Ep_c1 and myCAFs. The top 30 marker genes of myCAFs were used to construct a prognostic signature with a significant response to immunotherapy. Finally, experiments identified Complement C1s subcomponent (C1S), Decorin (DCN), and Neuroblastoma suppression of tumorigenicity 1 (NBL1) as potential ESCC risk-related genes. CONCLUSION: Our findings highlight the dynamic alterations in the post-NCRT ESCC microenvironment and provide a foundation for the development of personalized treatment and immunotherapeutic approaches. Future studies are warranted to further validate these findings and explore their clinical implications.