Spatial transcriptomics delineates molecular features and cellular plasticity in lung adenocarcinoma progression

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Lung adenocarcinoma (LUAD) exhibits coexisting indolent and aggressive histologic subtypes.
• The molecular basis for subtype transitions and heterogeneity in LUAD remains largely unknown.

Purpose of the Study:

• To elucidate the molecular characteristics and cellular plasticity of distinct LUAD histologic subtypes.
• To identify molecular drivers and signaling pathways associated with LUAD subtype progression.

Main Methods:

• Integration of spatial transcriptomics and multiplex immunohistochemistry.
• Analysis of transcriptional reprogramming and cell signaling dynamics.

Main Results:

• Distinct LUAD histologic subtypes display heterogeneity in dedifferentiation states.
• Hypoxia-induced regulatory networks significantly influence subtype progression.
• Specific tumor-associated macrophage subpopulations are identified within each LUAD subtype, potentially creating an immunosuppressive microenvironment.

Conclusions:

• A comprehensive molecular landscape of LUAD subtype progression has been established.
• The findings suggest novel therapeutic strategies and targets for invasive LUAD, particularly focusing on macrophage roles and hypoxia pathways.