Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer

Abstract

Abstract Background Histone lysine lactylation (Kla) is a newly identified histone modification, which plays a crucial role in cancer progression. Hence, we determined the prognostic value of Kla in breast cancer (BC). Methods We obtained RNA expression profiles of BC from The Cancer Genome Atlas (TCGA), following screening out Kla-specific genes. Furthermore, we determined the prognostic value of Kla by constructing a cox model based on Kla-specific genes. Subsequently, we identified expression of lactate accumulation-related genes and prognostic Kla-specific genes through Human Protein Atlas (HPA), and further performed a correlation analysis based on their expression. Meanwhile, we explored the effects of Kla on BC tumor microenvironment (TME), drug therapy and immunotherapy. Moreover, we predicted the pathways influenced by Kla via gene set enrichment analysis (GSEA). Results A total of 1073 BC samples and 112 normal controls were obtained from TCGA, and 23 tumor samples were removed owing to inadequate clinical information. We identified 257 differentially expressed Kla-specific genes (DEKlaGs) in BC. A cox model involved with CCR7, IGFBP6, NDUFAF6, OVOL1 and SDC1 was established, and risk score could be visualized as an independent biomarker for BC. Meanwhile, Kla was remarkably associated with BC immune microenvironment, drug therapy and immunotherapy. Kla was identified to be related to activation of various BC-related KEGG pathways. Conclusion In conclusion, Kla contributes to drug resistance and undesirable immune responses, and plays a crucial role in BC prognosis, suggesting that Kla was expected to be a new therapeutic target for BC.

Keywords

• Lactylation
• Kla
• Breast cancer
• Prognosis
• Immunotherapy