Identifying CTSF and GSTM3 as chemoresistance therapeutic targets in breast cancer through multi-omics MR analysis

Area of Science:

• Genetics
• Oncology
• Pharmacogenomics

Background:

• Breast cancer is a significant global health concern, with drug resistance posing a major obstacle to effective treatment.
• Identifying genetic factors influencing treatment response is crucial for personalized medicine in breast cancer.

Purpose of the Study:

• To identify novel genes associated with breast cancer risk and response to chemotherapy using integrated multi-omics data.
• To investigate the functional roles of candidate genes in chemoresistance and identify potential therapeutic targets.

Main Methods:

• Integration of genome-wide association studies (GWAS), expression quantitative trait loci (eQTL), and proteomic quantitative trait loci (pQTL) data.
• Application of Mendelian randomization to establish causal genetic associations.
• Functional studies to assess gene expression correlations with drug response and pathway enrichment analyses.

Main Results:

• CTSF and GSTM3 were identified as key candidate genes, showing consistent associations at both RNA and protein levels.
• CTSF expression was linked to taxane resistance and cyclophosphamide sensitivity.
• GSTM3 influenced response to multiple chemotherapy regimens, suggesting a broader role in chemoresistance.

Conclusions:

• CTSF and GSTM3 represent promising biomarkers for predicting breast cancer treatment outcomes.
• Targeting CTSF and GSTM3 may offer novel strategies to overcome chemoresistance in breast cancer therapy.