Recent large-scale multi-omics studies have characterized the heterogeneity of esophageal squamous cell carcinoma(ESCC),but inconsistent clinical management has hindered the identification of prognostic markers and pa...Recent large-scale multi-omics studies have characterized the heterogeneity of esophageal squamous cell carcinoma(ESCC),but inconsistent clinical management has hindered the identification of prognostic markers and patient stratification.Here,we conducted genomic and transcriptomic profiling of 203 patients from the ECTOP-2002 study with full clinical information.Mutation in the mucin family,as well as APOBEC signature,were associated with poor prognosis.In contrast,activation of the epithelial-keratinization(EpK)pathway was strongly linked to favorable prognosis and lower post-chemotherapy recurrence rates.Independent validation supported S100A8+S100A9 complex as a key marker of EpK pathway.Furthermore,we established a prognostic stratification system,FU-ESCC subtyping,which defines three subtypes with distinct molecular and clinical features.The EpK-activated subtype retained characteristics of healthy squamous epithelial cells,showed high expression of the S100A8+S100A9 complex,and was associated with favorable prognosis.展开更多
基金supported by National Key R&D Program of China(2022YFA1103900)National Natural Science Foundation of China(82430099)+1 种基金the Clinical Research Special Project of Shanghai Municipal Health Commission(202440070)the Medical Research Special Project for Shanghai Science and Technology Innovation Action Plan(24Y12800400).
文摘Recent large-scale multi-omics studies have characterized the heterogeneity of esophageal squamous cell carcinoma(ESCC),but inconsistent clinical management has hindered the identification of prognostic markers and patient stratification.Here,we conducted genomic and transcriptomic profiling of 203 patients from the ECTOP-2002 study with full clinical information.Mutation in the mucin family,as well as APOBEC signature,were associated with poor prognosis.In contrast,activation of the epithelial-keratinization(EpK)pathway was strongly linked to favorable prognosis and lower post-chemotherapy recurrence rates.Independent validation supported S100A8+S100A9 complex as a key marker of EpK pathway.Furthermore,we established a prognostic stratification system,FU-ESCC subtyping,which defines three subtypes with distinct molecular and clinical features.The EpK-activated subtype retained characteristics of healthy squamous epithelial cells,showed high expression of the S100A8+S100A9 complex,and was associated with favorable prognosis.
