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Integrative Multi-omics Analysis and Mendelian Randomization Reveal Potential Therapeutic Targets and their

Youpeng Chen1, Enzhong Li2, Zhenglin Chang1

  • 1State Key Laboratory of Respiratory Disease, Department of Clinical Laboratory, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, 510140, China.

Current Medicinal Chemistry
|February 12, 2025
PubMed
Abstract

Insights

This study identifies 23 novel therapeutic targets for Lung Squamous Cell Carcinoma (LUSC) by analyzing gene expression and patient data. These findings offer new avenues for LUSC treatment strategies.

Area of Science:

  • Oncology
  • Genomics
  • Immunology

Background:

  • Lung Squamous Cell Carcinoma (LUSC) is a major non-small cell lung cancer subtype with limited targeted therapy options.
  • Identifying novel therapeutic targets is crucial for improving LUSC treatment strategies.

Purpose of the Study:

  • To identify and characterize novel prognostic and therapeutic targets for LUSC.
  • To explore the functional roles and expression patterns of these targets within the LUSC tumor microenvironment.

Main Methods:

  • Utilized bulk RNA sequencing, Weighted Gene Co-expression Network Analysis (WGCNA), survival analysis, and Mendelian Randomization (MR) to identify prognostic genes.
  • Employed LASSO regression, Protein-Protein Interaction (PPI) network analysis, and immune infiltration assessments to evaluate therapeutic potential.
  • Conducted pathway enrichment analysis, single-cell RNA sequencing (scRNA-seq), and pseudotime analysis to understand gene functions and cell-specific expression.

Main Results:

  • Identified 23 prognostically significant therapeutic targets for LUSC, categorized into tier-one, tier-two, and tier-three genes.
  • Functional enrichment revealed significant roles in immune response regulation, including T-cell receptor signaling and the complement system.
  • scRNA-seq and pseudotime analyses elucidated cell-type-specific expression patterns and cellular heterogeneity within the LUSC microenvironment.

Conclusions:

  • Successfully identified a set of 23 novel therapeutic targets for LUSC.
  • Highlighted the importance of immune-related pathways and cell-specific gene expression in LUSC pathogenesis.
  • These identified genes represent promising candidates for future therapeutic development in LUSC.
Keywords:
Lung squamous cell carcinomabulk RNA sequencingeQTL datasets.mendelian randomizationpotential therapeutic targetssingle-cell RNA sequencing

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