Hypermethylated KLF9 is an independent prognostic factor for favorable outcome in breast cancer

Abstract

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.