Background and objective: Breast cancer (BC) is the most lethal human malignancy and is the leading cause of cancer-associated death in women worldwide. Krüppel-like factor 9 (KLF9 ) belongs to a family of transcriptional regulators and its role in BC has not been fully investigated.
Method: Data mining was used to analyze BC data from The Cancer Genome Atlas (TCGA) database, which was downloaded using the UCSC Xena browser. The differential expression and methylation level of KLF9  was analyzed in patients with BC and corresponding normal controls enrolled from our hospital. Besides, the correlation of KLF9  methylation and prognosis was explored, and gene set enrichment analysis (GSEA) was conducted to identify the potential signaling pathway of KLF9  involved.
Results: Both TCGA and BC tissues indicated hypermethylation of the KLF9  promoter region in patients with BC compared with normal controls, which might account for the dysregulation of KLF9  in patients with BC. Besides, hypermethylation of KLF9  was detected in patients with estrogen or progesterone receptor-positive and non-triple-negative disease. Further, hypermethylation of KLF9  was demonstrated to be a potential independent biomarker in obtaining favorable outcomes in BC. By GSEA, tumor-associated biological processes and signaling pathway were identified, which indicated that KLF9  might play a vital role in the carcinogenesis of BC.
Conclusion: KFL9  plays an important role in the carcinogenesis of BC through the multiple tumor-associated signaling pathway. The hypermethylation of KLF9  resulted in its reduced expression in BC, while the hypermethylation of KLF9  has potential in the prediction of favorable outcomes in BC.
Keywords: Krüppel-like factor 9 , methylation, breast cancer, prognostic biomarker, GSEA