Keratin 80 serves as a potential biomarker in metastatic breast cancer.

BACKGROUND: Breast cancer (BC) is the most common type of female cancer with alarmingly high morbidity and mortality, especially metastatic BC (mBC). OBJECTIVE: Our object is to explore a potential prognostic biomarker for mBC. The RNA-seq data of BC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. METHODS: The identification of candidate genes was achieved through the WGCNA, differentially expressed gene analysis and protein-protein interaction network. The prognostic predictive performance of the hub gene, Keratin 80 (KRT80), was evaluated through the Kaplan-Meier and multivariate Cox regression analysis. Validation of the expression of KRT80 in BC cell lines was carried out using qPCR and western blot experiments. The functional role of KRT80 in BC was further examined through loss- and gain-of-function assays in vitro. RESULTS: The results from the public database indicated a significant increase in KRT80 expression within the mBC group when compared to the primary BC group, and also heightened KRT80 levels were observed in BC tissues relative to the control group. Meanwhile, ROC curve analysis demonstrated the potential diagnostic potential of KRT80 for mBC. Notably, elevated KRT80 levels were found to be an independent predictor of unfavorable prognosis for BC patients. GSEA analysis demonstrated the involvement of KRT80 in NF-kappa B signaling pathway. Furthermore, the results of immune cell infiltration analysis revealed a marked negative correlation between KRT80 expression and CD8 T cells, activated NK cells. Drug sensitivity analysis showed that patients with high expression of KRT80 may exhibit increased sensitivity to Lapatinib. Functionally, overexpression of KRT80 facilitated the viability, migration, invasion and epithelial-mesenchymal transition (EMT) in BT549 cells, a metastatic BC cell line. CONCLUSION: Collectively, KRT80 may be linked with metastasis of BC, and it may serve as a potential therapeutic target for mBC treatment.