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Identification of biomarkers and potential drug targets for esophageal cancer: a Mendelian randomization study.

Chengjun Li1, Xiaomeng Cui2, Mudan Ren1

  • 1Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

Scientific Reports
|March 10, 2025
PubMed
Summary

This study used Mendelian Randomization to find new drug targets for esophageal cancer (EC). Five proteins were linked to EC risk, with HPSE and GNRH2 showing protective effects, suggesting potential therapeutic avenues.

Keywords:
CausalityDrug targetDruggable geneEsophageal cancerMendelian randomizationPlasma protein

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Area of Science:

  • Genetics and Genomics
  • Oncology
  • Pharmacology

Background:

  • Esophageal cancer (EC) presents a significant global health challenge with limited effective treatment options and poor patient outcomes.
  • Identifying novel therapeutic targets is crucial for improving EC management and patient prognosis.

Purpose of the Study:

  • To leverage Mendelian Randomization (MR) to identify potential protein-based drug targets for esophageal cancer.
  • To investigate the causal relationships between plasma proteins and EC risk using genetic data.

Main Methods:

  • Two-sample MR analysis was performed on 734 plasma proteins and 4,479 druggable genes.
  • Inverse variance weighted (IVW) method was primary, supported by Steiger filtering, heterogeneity/pleiotropy tests, SMR, and Bayesian co-localization analysis.
  • DrugBank database was used to identify drugs associated with candidate proteins.

Main Results:

  • Five proteins (HPSE, ST3GAL1, CEL, KLK13, GNRH2) showed significant associations with EC risk.
  • HPSE and GNRH2 exhibited protective effects (ORs < 1), while ST3GAL1, CEL, and KLK13 were associated with increased EC risk (ORs > 1).
  • HPSE demonstrated moderate co-localization with EC, and sensitivity analyses confirmed no significant heterogeneity or pleiotropy.

Conclusions:

  • The identified proteins, particularly HPSE and GNRH2, represent promising therapeutic targets for esophageal cancer.
  • Further clinical investigation of these protein targets is warranted to develop novel EC treatments.