Single-cell analysis identified POSTN⁺ cells associated with the aggressive phenotype and risk of esophageal squamous cell carcinoma

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Tumors are complex and heterogeneous, with diverse cancer cell populations.
• Esophageal squamous cell carcinoma (ESCC) presents a significant challenge due to its aggressive nature.

Purpose of the Study:

• To delineate aggressive epithelial subpopulations in ESCC using single-cell analysis.
• To identify key genes and genetic variants associated with ESCC aggressiveness and risk.

Main Methods:

• Employed the Scissor algorithm for single-cell analysis to identify distinct cell subpopulations.
• Analyzed gene expression profiles, focusing on pathways like epithelial-mesenchymal transition and PI3K-Akt.
• Investigated expression quantitative trait loci (eQTLs) of signature genes for ESCC risk prediction.
• Conducted functional annotation, replication analyses, and biochemical experiments.

Main Results:

• Identified an aggressive epithelial subpopulation in ESCC with elevated expression of genes like CAV1, COL3A1, COL6A1, POSTN, and TAGLN.
• POSTN expression was significantly upregulated during tumorigenesis and progression.
• A specific POSTN promoter variant (rs1028728) was strongly associated with increased ESCC risk.
• The rs1028728[T] allele enhances POSTN expression by influencing PRRX1 binding.

Conclusions:

• Single-cell analysis successfully delineated an invasive epithelial subpopulation in ESCC.
• POSTN is a crucial marker for the aggressive phenotype in ESCC and a potential predictor of risk.
• Findings provide insights into ESCC prevention and intervention strategies.