Background
Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype; most cases are triple-negative breast cancers (TNBCs) and are poorly responsive to conventional systemic therapy. Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered. We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC.
Conclusion
Our research indicated that KLK5 may be a pivotal molecule with a key role in the mechanism of tumorigenesis in metaplastic TNBC.
Methods
Differentially expressed genes (DEGs) in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407. The GSE76275 data set and The Cancer Genome Atlas (TCGA) database were used to screen DEGs in TNBC and non-TNBC. Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis of DEGs. Online databases, including UALCAN, GEPIA, HPA, Breast Cancer Gene-Expression Miner, and quantitative PCR and western blot, were used to examine KLK5 messenger RNA and protein expression in breast cancer. Analysis of KLK5‑associated genes was performed with TCGA data, and the LinkedOmics database was used to detect the genes co-expressed with KLK5. STRING (Search Tool for the Retrieval of Interacting Genes) and Cytoscape were used to screen for hub genes. Kaplan‑Meier plotter was used for survival analysis.
Results
KLK5 was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC. The KLK5 gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC. KEGG and GO analyses revealed that epithelial-to-mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which KLK5 and its associated genes DSG1 and DSG3 influence metaplastic TNBC progression. Prognosis analysis showed that only low expression of KLK5 in metaplastic TNBC had clinical significance.