Spatial and single-cell transcriptomic profiling reveals interplay between SRGN-associated epithelial programs and
Shengqiang Mao1, Chunwei Pang2, Hong Hang1
1Department of Respiratory and Critical Care Medicine, Frontiers Science Center for Disease-Related Molecular Network, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Journal of Translational Medicine
|May 23, 2026
Summary
Researchers mapped lung adenocarcinoma (LUAD) progression from early lesions to invasive cancer. They found elevated SRGN expression and specific macrophage interactions drive tumor growth, offering new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Understanding lung adenocarcinoma (LUAD) progression is key for early detection and treatment.
- Mapping the molecular and cellular changes from precursor lesions to invasive cancer is crucial.
Purpose of the Study:
- To map the evolutionary trajectory of LUAD from precursor lesions to invasive adenocarcinoma.
- To identify molecular and cellular mechanisms driving LUAD progression.
Main Methods:
- Integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics.
- Analyzed four histologic stages: AAH, AIS, MIA, and IAC.
- Validated findings in a stage-specific A/J mouse model.
Main Results:
- Identified a tumor-intrinsic program with elevated SRGN expression linked to EMT and proliferation.
- Observed stage-dependent accumulation of C1QC+ macrophages.
- Found close spatial positioning and enhanced interactions between SRGN+ malignant cells, macrophages, and exhausted T cells via specific ligand-receptor pairs (MIF-LIFR, ADAM17-ERBB4, OSM-EGFR, OSM-TNFRSF14).
Conclusions:
- A coordinated epithelial-macrophage module drives LUAD progression.
- SRGN and its spatial interactions are potential targets for early therapeutic intervention and diagnostic modeling.
