Spatial Dynamics of Tumor Cell Plasticity in Lung Adenocarcinoma Revealed by Region-Specific Single Cell...

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Tumor cell plasticity is crucial for cancer progression and treatment resistance.
• Understanding the spatial dynamics of plasticity, such as epithelial-mesenchymal transition (EMT) and stemness, is vital but poorly understood in lung adenocarcinoma (LUAD).

Purpose of the Study:

• To investigate the spatial distribution of EMT and stemness in LUAD.
• To determine the prognostic relevance of these plasticity features and identify associated biomarkers.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was performed on LUAD tumor fragments from different regions (core, core-adjacent, edge).
• Stemness was assessed using CytoTRACE2, EMT using UCell and Hallmark gene signatures.
• Prognostic relevance was evaluated using Scissor, and key genes were validated via immunohistochemistry.

Main Results:

• LUAD exhibits significant spatial heterogeneity in tumor cell plasticity.
• Stemness potential was higher at the tumor edge, whereas EMT was more prominent in the core.
• Higher EMT scores correlated with poor overall survival, and stemness with poor progression-free survival.
• MYC-targets v1 signature genes PCBP1 and PA2G4 were identified as potential biomarkers for poor prognosis and were localized in tumor cells.

Conclusions:

• Tumor cell plasticity features display distinct spatial patterns within LUAD.
• EMT and stemness are spatially segregated and have differential prognostic implications.
• PCBP1 and PA2G4 represent promising biomarkers for predicting poor prognosis in LUAD.