Single-cell and spatial transcriptomic profiling of POU5F1 in Lung Adenocarcinoma: Dynamics, spatial niche, and...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• POU5F1 (OCT4) is a key pluripotency regulator implicated in tumor stemness and immune microenvironment modulation.
• The specific role and mechanisms of POU5F1 in lung adenocarcinoma (LUAD) remain inadequately understood.

Purpose of the Study:

• To systematically investigate the comprehensive function and underlying mechanisms of POU5F1 in LUAD.
• To evaluate POU5F1 as a potential prognostic biomarker and therapeutic target in LUAD.

Main Methods:

• Integrated genetic causality inference, single-cell and spatial transcriptomics, RNA velocity, and machine learning.
• Summary-based Mendelian Randomization (SMR) linked GWAS with lung tissue eQTL data.
• In vitro experiments validated POU5F1's biological functions, including its effects on proliferation, migration, invasion, and apoptosis.

Main Results:

• POU5F1 showed genetic association with lung cancer risk and was enriched in stem-like LUAD cells.
• Spatial analysis revealed POU5F1+ tumor cells co-localized with cancer-associated fibroblasts (CAFs).
• A POU5F1-related gene signature predicted LUAD prognosis and correlated with immune suppression and targeted therapy response. POU5F1 knockdown inhibited LUAD cell growth and induced apoptosis via the Bcl-2/caspase-3 pathway, EMT modulation, and Nanog downregulation.

Conclusions:

• POU5F1 significantly promotes LUAD progression by sustaining stemness, reprogramming CAFs, and facilitating immune evasion.
• POU5F1 emerges as a potential prognostic biomarker and a promising therapeutic target for LUAD.