Integrated summary data-based Mendelian randomization and colocalization analysis reveals TNNT3 as a target of Deer-Antler-Ginseng-formula for triple-negative breast cancer

As an aggressive tumor type with poor prognosis, high recurrence and metastasis tendency, and lack of effective therapeutic targets, triple-negative breast cancer (TNBC) not only poses a remarkable treatment challenge, but also necessitates continuous exploration of new therapy targets. We used Summary data-based Mendelian Randomization (SMR) analysis, Colocalization (Coloc) analysis, and comprehensive gene expression analysis to probe deep into the genetic causal correlation between the therapeutic target genes of Deer-Antler-Ginseng-Formula (DAGF) and TNBC, and conducted animal experiments to detect the protein expression of the identified drug targets. First and foremost, 1471 drug-target genes of DAGF were retrieved from the TCMSP and BATMAN-TCM databases. Subsequent to the intersection with the differentially expressed genes of breast cancer in TCGA, 221 target genes of DAGF were selected for more comprehensive and systematic analysis. As evidently demonstrated by SMR analysis, 9 genes were genetically causally linked to TNBC. It is particularly noteworthy that 6 genes revealed a negative association with TNBC; 3 genes suggested a positive correlation with TNBC. Nonetheless, nothing more than SPTBN1, PTGFR, and TNNT3 passed the coloc analysis, which demonstrated a significant genetic association with TNBC. Subsequent gene-expression verification and animal experimental models demonstrated TNNT3 is the potential drug target of DAGF for TNBC. This study demonstrates that DAGF functions as an inhibitor of tumor growth in TNBC xenograft models, with preliminary evidence identifying TNNT3 as a potential therapeutic target. These findings offer novel strategic avenues for breast cancer treatment.