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Identifying potential therapeutic targets in lung adenocarcinoma: a multi-omics approach integrating bulk and single-cell RNA sequencing with Mendelian randomization

Authors :
Youpeng Chen
Enzhong Li
Zhenglin Chang
Tingting Zhang
Zhenfeng Song
Haojie Wu
Zhangkai J. Cheng
Baoqing Sun
Source :
Frontiers in Pharmacology, Vol 15 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

Our research aimed to identify new therapeutic targets for Lung adenocarcinoma (LUAD), a major subtype of non-small cell lung cancer known for its low 5-year survival rate of 22%. By employing a comprehensive methodological approach, we analyzed bulk RNA sequencing data from 513 LUAD and 59 non-tumorous tissues, identifying 2,688 differentially expressed genes. Using Mendelian randomization (MR), we identified 74 genes with strong evidence for a causal effect on risk of LUAD. Survival analysis on these genes revealed significant differences in survival rates for 13 of them. Our pathway enrichment analysis highlighted their roles in immune response and cell communication, deepening our understanding. We also utilized single-cell RNA sequencing (scRNA-seq) to uncover cell type-specific gene expression patterns within LUAD, emphasizing the tumor microenvironment’s heterogeneity. Pseudotime analysis further assisted in assessing the heterogeneity of tumor cell populations. Additionally, protein-protein interaction (PPI) network analysis was conducted to evaluate the potential druggability of these identified genes. The culmination of our efforts led to the identification of five genes (tier 1) with the most compelling evidence, including SECISBP2L, PRCD, SMAD9, C2orf91, and HSD17B13, and eight genes (tier 2) with convincing evidence for their potential as therapeutic targets.

Details

Language :
English
ISSN :
16639812
Volume :
15
Database :
Directory of Open Access Journals
Journal :
Frontiers in Pharmacology
Publication Type :
Academic Journal
Accession number :
edsdoj.42ef13c3b11143e4a3e57f9b3f058443
Document Type :
article
Full Text :
https://doi.org/10.3389/fphar.2024.1433147