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Multiomic Mendelian randomization analysis of metabolic gene methylation expression and protein levels in lung adenocarcinoma

  • 0Department of Thoracic Surgery, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
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September 29, 2025

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September 29, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study reveals key metabolic genes linked to lung adenocarcinoma (LUAD) risk. Methylation, expression, and protein levels of genes like CHRNA3, FLOT1, HYKK, and POGLUT3 offer potential targets for early LUAD detection and treatment.

Area Of Science

  • Oncology
  • Genetics
  • Metabolism

Background

  • Metabolic reprogramming is a key factor in lung adenocarcinoma (LUAD) development.
  • Understanding the interplay between metabolic gene alterations and LUAD risk is crucial for early detection and treatment strategies.

Purpose Of The Study

  • To investigate the associations between metabolic gene methylation, expression, and protein levels with LUAD risk.
  • To leverage multi-omic data and Mendelian randomization to identify potential molecular targets for LUAD.

Main Methods

  • Utilized summary-level data from methylation, expression, and protein quantitative trait loci (QTL) studies.
  • Employed Mendelian randomization and colocalization analyses to assess causal relationships between metabolic gene features and LUAD risk.
  • Validated findings using discovery data from the TRICL Consortium and the FinnGen cohort.

Main Results

  • Identified significant associations between LUAD risk and molecular features of metabolic genes, including CHRNA3 methylation, FLOT1 and HYKK expression, and POGLUT3 protein levels.
  • CHRNA3 methylation showed a strong association with increased LUAD risk, with validation in an independent cohort.
  • FLOT1 and HYKK expression were moderately associated with LUAD risk, while POGLUT3 protein levels demonstrated a protective effect.

Conclusions

  • This multi-omic Mendelian randomization study confirms the involvement of specific metabolic genes in LUAD risk.
  • Methylation changes in CHRNA3, expression of FLOT1 and HYKK, and protective POGLUT3 protein levels are key molecular features associated with LUAD susceptibility.
  • These findings highlight potential molecular targets for early LUAD detection and novel therapeutic strategies.

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