Integrating multi-omics data of Triple-Negative Breast Cancer to explore the role of Kynurenine pathway and KYNU as a therapeutic target.

BACKGROUND

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer with poor prognosis. TNBC currently lacks effective therapeutic options, and its molecular mechanisms are still unclear. Thus, identifying novel molecular targets may offer insights to enhance treatment strategies. Accumulating evidence suggests the key role of the kynurenine pathway (KP) of the tryptophan metabolism in the pathogenesis of tumor diseases. The KP is the primary route of tryptophan metabolism, accounting for over 95 % of tryptophan catabolism. Genes within the KP have been implicated in tumor promotion, although their functional mechanisms remain to be elucidated.

METHODS

Bioinformatics approaches were employed to analyze the expression and function of all genes within the KP in TNBC.

RESULTS

Genes of the KP were found to be upregulated in TNBC and associated with adverse outcomes. These genes were predominantly involved in various biosynthetic functions. Correlation analyses revealed a close association between KP genes and markers of inflammatory pathways, as well as with chemoresistance in tumors. Immunofluorescence revealed that KYNU accumulated in the nucleus and at sites of nuclear chromatin in TNBC cells.

CONCLUSION

Genes of the KP are correlated with the progression and drug resistance of TNBC, but further research is needed to clarify the underlying molecular mechanisms.