Bioinformatics Validation of the Prognostic Significance of Zbtb46 and Related Transcription Factors in Immunotherapy of Breast Cancer in Female Athletic Players and Fitness Enthusiasts

Abstract

ZBTB46, known for its high expression in human dendritic cells (DCs) and role as a specific transcription factor exclusive to DCs, has been shown to mitigate the inflammatory properties of ILC3. Research indicates that DC functionality significantly impacts breast cancer (BC) responses to chemotherapy, with ZBTB46 playing a pivotal role in the neuroendocrine regulation of prostate cancer, contributing to the drug resistance mechanisms of castration-resistant prostate cancer, and influencing disease progression. However, the association between ZBTB46-related transcription factors (TFs) and BC, particularly in female athletic players and fitness enthusiasts, remains to be elucidated. Utilizing the GEO (Gene Expression Omnibus) dataset (GSE181865) and the Limma package in R software, we identified 16,954 differentially expressed genes (DEGs), with 13,818 up-regulated and 14,878 down-regulated by at least 1-fold. The top 20 genes exhibiting significant expression changes were selected for further analysis. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, ZBTB46 was hypothesized to contribute to BC's inflammatory progression by influencing tumor-associated DCs and modulating BC progression and migration through neuroendocrine regulation and oxidative phosphorylation. Our investigation also highlighted a crucial link between ZBTB46-associated TFs—IL-16, CLEC7A, and PIPK3—and BC. Non-negative matrix factorization (NMF) was applied to cluster the top 100 DEGs, revealing that Asian BC patients in Clusters 1, 2, and 4 had significantly longer survival times and better prognoses compared to those in Cluster 3 (P<0.05). ZBTB46's connection to BC immunotherapy prognosis was underscored, leading to the construction of a 17 TF signature gene model to forecast BC outcomes. In conclusion, our findings propose that ZBTB46 and its related TFs may affect BC immunotherapy prognosis by modulating BC's neuroendocrine functions, offering valuable insights into potential therapeutic targets and prognostic indicators for BC, particularly in female athletes and fitness devotees.