2023 World Conference on Lung Cancer (Posters)-EP02.02. Identification of COL5A2+ Cancer-Associated Fibroblast in Solid Subtype of LUAD by Integrated Analysis of WGCNA and Single Cell RNA-seq

EP02.02. Identification of COL5A2+ Cancer-Associated Fibroblast in Solid Subtype of LUAD by Integrated Analysis of WGCNA and Single Cell RNA-seq - PDF(Slides)

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In this study, the researchers aimed to understand the underlying mechanisms contributing to the clinical features of solid predominant lung adenocarcinoma (LUAD). They used two datasets - a single-cell RNA sequencing (scRNA-seq) dataset from Bischoff et al. and a microarray dataset from Zabeck et al. They performed weighted correlation network analysis (WGCNA) and identified four fibroblast subpopulations, with one subpopulation called Fibro-C4 showing significant enrichment in cases of solid predominant LUAD.<br /><br />Using Monocle2, the researchers found that Fibro-C4 originated from normal fibroblast differentiation and were situated at the terminal stage of differentiation. They also performed WGCNA on the microarray dataset and identified the Greenyellow module, which showed a positive correlation with solid predominant LUAD.<br /><br />Furthermore, they identified hub genes associated with solid predominant LUAD, including COL5A2, THBS2, COL4A2, COL6A2, and COL15A1. High expression of COL5A2 was associated with poor overall survival. The researchers verified the significance of COL5A2 in solid predominant LUAD using multiple datasets.<br /><br />The researchers compiled the major cell types within solid LUAD and conducted an analysis of cell communication using a tool called cellchat. They found that Fibro-C4 had strong interactions with exhausted T cells and regulatory T cells through the CXCL9/10-CXCR3 pathway.<br /><br />Overall, the study identified a subset of fibroblasts expressing ECM markers, chemokines, and tryptophan catabolic enzymes, particularly COL5A2. These cancer-associated fibroblasts (CAFs) were associated with poor prognosis and promoted the formation of an immunosuppressive microenvironment in solid predominant LUAD. This research provides insights into the mechanisms underlying the clinical features of solid LUAD and highlights potential therapeutic targets.

Asset Subtitle

Zhaoxuan Wang

Meta Tag

Speaker Zhaoxuan Wang

Topic Tumor Biology: Preclinical Biology - Omics Approaches

Keywords

solid predominant lung adenocarcinoma

underlying mechanisms

clinical features

single-cell RNA sequencing

microarray dataset

weighted correlation network analysis

fibroblast subpopulations

Monocle2

hub genes

cell communication