Prioritization of therapeutic targets for cancers using integrative multi-omics analysis

Hum Genomics. 2024 Apr 24;18(1):42. doi: 10.1186/s40246-024-00571-2.

Abstract

Background: The integration of transcriptomic, proteomic, druggable genetic and metabolomic association studies facilitated a comprehensive investigation of molecular features and shared pathways for cancers' development and progression.

Methods: Comprehensive approaches consisting of transcriptome-wide association studies (TWAS), proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) and MR were performed to identify genes significantly associated with cancers. The results identified in above analyzes were subsequently involved in phenotype scanning and enrichment analyzes to explore the possible health effects and shared pathways. Additionally, we also conducted MR analysis to investigate metabolic pathways related to cancers.

Results: Totally 24 genes (18 transcriptomic, 1 proteomic and 5 druggable genetic) showed significant associations with cancers risk. All genes identified in multiple methods were mainly enriched in nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Additionally, biosynthesis of ubiquinol and urate were found to play an important role in gastrointestinal tumors.

Conclusions: A set of putatively causal genes and pathways relevant to cancers were identified in this study, shedding light on the shared biological processes for tumorigenesis and providing compelling genetic evidence to prioritize anti-cancer drugs development.

Keywords: Cancers; Genome-wide association studies; Multi-omics; NRF2 pathway; Therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Metabolic Networks and Pathways / genetics
  • Metabolomics / methods
  • Multiomics
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / pathology
  • Proteomics
  • Transcriptome / genetics

Substances

  • NF-E2-Related Factor 2