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pmid:38090381
Bioinformatics analysis of human kallikrein 5 (KLK5) expression in metaplastic triple-negative breast cancer.
Yue Song · Guiying Bai · Xiaoqing Li · Liyan Zhou · Yiran Si · Xiaohui Liu · Yilin Deng · Yehui Shi
Cancer innovation · 2023 doi:10.1002/cai2.96
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Experiment
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Complete file
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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.\nMethods: 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.\nResults: 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.\nConclusion: Our research indicated that KLK5 may be a pivotal molecule with a key role in the mechanism of tumorigenesis in metaplastic TNBC.", "claims": [{"id": "claim-data-access", "statement": "All data generated or analyzed on the basis of public databases in this study were obtained from the databases mentioned in the methods, and relevant descriptions and website links are included in this article. 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The PCR and western blot results were derived from at least three ind"], "order_basis": "paper_text_order:1103", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d organs from normal or diseased cases using RNAseq analysis and immunohistochemistry. KLK5 expr", "des easy access to publicly available cancer transcriptome data including TCGA [19]. GEPIA is a new web", "://www.proteinatlas.org/) contains the human transcriptomic and proteomic data in cells, tissues, and or", "le of KLK5 in breast cancer, we compared the transcriptomes of the KLK5‐high and KLK5‐low groups using T"], "order_basis": "paper_text_order:2401", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["or diseased cases using RNAseq analysis and immunohistochemistry. KLK5 expression was analyzed in various bre"], "order_basis": "paper_text_order:2962", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["analysis of variance"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}