Proteome-wide mendelian randomization study implicates therapeutic targets in common cancers

Area of Science:

• Genetics and Genomics
• Oncology
• Pharmacology

Background:

• Growing interest in targeted cancer therapies highlights limitations in early diagnosis and treatment.
• Urgent need for novel drug targets and effective therapeutic strategies in oncology.

Purpose of the Study:

• To identify novel plasma protein targets for site-specific cancers using genetic association analysis.
• To explore the therapeutic potential of identified proteins and their interaction with existing cancer drug targets.

Main Methods:

• Combined cis-Mendelian randomization (cis-MR) and colocalization analysis of 732 plasma proteins.
• Validation using the UK Biobank dataset and construction of a protein-protein interaction network.

Main Results:

• Identified associations between plasma proteins and prostate, breast, and lung cancers.
• Highlighted KDELC2, TNFRSF10B, CPNE1, PDIA3, SPINT2, GSTP1, CTSS, GDI2, ISLR2, CTSF, SFTPB, ICAM5, and FLRT3 as potential therapeutic targets.
• TNFRSF10B, GSTP1, and PDIA3 interact with targets of existing cancer medications.

Conclusions:

• Thirteen plasma proteins show potential as therapeutic targets for prostate, breast, and lung cancers.
• Further research into proteins such as KDELC2, TNFRSF10B, CPNE1, and PDIA3 may lead to more effective cancer treatments.