Single-cell and Bulk RNA-Seq reveal angiogenic heterogeneity and microenvironmental features to evaluate prognosis...

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Angiogenesis is a key factor in lung adenocarcinoma (LUAD) progression and influences the tumor microenvironment (TME).
• Understanding the role of angiogenesis in LUAD prognosis and its clinical applications is crucial for effective treatment.
• Its precise mechanisms within the TME and impact on patient outcomes require further elucidation.

Purpose of the Study:

• To investigate the heterogeneity of angiogenesis in LUAD using integrated single-cell and bulk transcriptome sequencing.
• To identify distinct angiogenic clusters and their associated TME features.
• To develop prognostic models for LUAD based on angiogenic factors.

Main Methods:

• Integrated single-cell and bulk transcriptome sequencing.
• Consensus clustering, Monocle2, pyscenic, and Cellchat algorithms.
• Univariate Cox and LASSO regression for prognostic model development, validated by IHC.
• Utilized CTRP 2.0 and PRISM databases for drug sensitivity analysis.

Main Results:

• Identified two distinct angiogenic clusters in LUAD, with one associated with poor prognosis and a pro-cancerous TME.
• Discovered three differentiated states of malignant epithelial LUAD cells with varying angiogenic activation, regulon submodules, and TME crosstalk.
• Validated SLC2A1's role in promoting LUAD angiogenesis and established the prognostic value of the Angiogenesis-related Score (ARS).
• Demonstrated that low ARS correlates with immunotherapy benefits, while high ARS indicates sensitivity to 15 chemotherapeutic agents.

Conclusions:

• Angiogenic clusters provide insights into LUAD prognosis and TME characteristics.
• Developed angiogenic prognostic models can predict LUAD prognosis, immunotherapy response, and chemotherapeutic drug sensitivity.