Single-cell profiling reveals that SAA1+epithelial cells promote distant metastasis of esophageal squamous cell carcinoma

IntroductionEsophageal squamous cell carcinoma (ESCC) is one of the most common cancers globally, with significant cell heterogeneity and poor prognosis. Distant metastasis in ESCC is one of the key factors that affects the prognosis of patients. Methods and resultsStarting with the analysis of ESCC single-cell sequencing data, we constructed a single-cell atlas of ESCC in detail and clarified the cell heterogeneity within tumor tissues. Through analysis of epithelial-mesenchymal transition (EMT) levels, gene expression, and pathway activation, we revealed the existence of a novel subpopulation of SAA1+ malignant cells in ESCC that are highly aggressive and closely associated with distant metastasis of ESCC. In vitro wound healing and transwell assays confirmed a strong invasion capacity of ESCC tumor cells with high expression of SAA1. Then, we constructed an effective and reliable prediction model based on the gene expression pattern of SAA1+ malignant cell subpopulations and confirmed that patients in the high-risk group had significantly worse prognosis than those in the low-risk group in the training cohort, internal verification cohort and external verification cohort. DiscussionThis manuscript contributes to exploration of the heterogeneity of ESCC tumor tissues and the search for new ESCC subpopulations with special biological functions. These results contribute to our understanding of the underlying mechanisms of distant metastasis of ESCC and thus provide a theoretical basis for improved therapies.

Automated summary

This study constructed a single-cell atlas of ESCC and revealed a novel subpopulation of SAA1+ malignant cells that are closely associated with distant metastasis of ESCC. A prediction model based on the gene expression pattern of SAA1+ cells was also established to identify high-risk patients with worse prognosis. These findings enhance our understanding of the mechanisms underlying distant metastasis in ESCC and provide a theoretical basis for improved therapies.