PD01.01. The Invisible Residue After Visible Cure: Hidden Malignant Traits Challenge Organ Preservation in ESCC

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ID: 325777
2026
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Ranked #161 of 453 articles by views in diseases of the esophagus : official journal of the international society for diseases of the esophagus

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Abstract
Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background Pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is increasingly used to guide organ-preservation strategies in esophageal squamous cell carcinoma (ESCC). However, a subset of patients relapse despite histological clearance. We hypothesized that molecularly malignant epithelial programs may persist even after pathological eradication. Methods Single-cell RNA sequencing was performed on 14 ESCC specimens, including nine treatment-naïve tumors and five post-nCRT tissues confirmed as pCR. After quality control and batch correction, 75,217 high-quality cells were analyzed, including 11,689 epithelial cells. Genomic instability was assessed using inferCNV-derived CNV scores. Stemness signatures were evaluated based on established regulators. Malignant pathway activity was quantified using Hallmark gene sets and published adaptive transcriptional modules. Pseudotime trajectory analysis was conducted to define transcriptional states of residual epithelial cells. Results Although epithelial cells were sparse in pCR specimens, residual epithelial populations were detectable. These cells exhibited significantly elevated CNV scores compared with pre-treatment tumor cells, suggesting persistent genomic instability. Stemness analysis demonstrated marked enrichment of self-renewal-associated regulators. Pathway analysis revealed sustained activation of EMT, hypoxia, TNFα–NF-κB signaling, angiogenesis, and stress-adaptive programs. Adaptive transcriptional modules were consistently upregulated. Trajectory analysis indicated that residual epithelial cells occupied a distinct terminal state enriched for therapy-adaptive and malignant programs. Conclusion Pathological complete response does not necessarily equate to molecular eradication. Residual epithelial cells in pCR tissues retain malignant and adaptive transcriptional programs, representing a potential biological reservoir for recurrence. These findings challenge reliance on histopathology alone and underscore the need to define molecular remission criteria before safely implementing organ-preservation strategies in ESCC.
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Authors Chenqiang Li, Tong Lu, Yuqin Cao, Hecheng Li
Journal diseases of the esophagus : official journal of the international society for diseases of the esophagus
Year 2026
DOI
10.1093/dote/doag077.071
URL
https://doi.org/10.1093/dote/doag077.071
Keywords Keywords not found

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