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Breast cancer (BC) is the most common type of malignancy among females worldwide. Histone modifications, which are the major post-translational modifications, have a significant role in cancer development and prognosis. However, whether histone family genes may serve as potential prognostic biomarkers for BC patients has remained elusive. In the present study, RNA-sequencing data were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes were identified and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analysis was performed. As histone family genes have been reported to be associated with cervical cancer, the present study hypothesized that histone family genes are associated with gynecological tumors. Histone family genes, including histone cluster 1 H1A family member B (HIST1H1B), HIST1H2AJ, HIST1H2AM, HIST1H2BI, HIST1H2BO, HIST1H3B, HIST1H3F, HIST1H3H, HIST1H4C and HIST1H4D , were upregulated and identified as hub genes in the protein-protein interaction network. In addition, Oncomine and the Human Protein Atlas were used to further verify the expression levels of histone gene sets. The PrognoScan database was then used to investigate the association between expression and prognostic value regarding cancer patient survival. The present results indicated that higher expression of histone gene sets was associated with poor overall survival, relapse-free survival and distant metastasis-free survival of BC patients. The differential expression of histone family genes between BC and normal samples was validated by reverse transcription-quantitative PCR. Finally, to determine the clinical role of histone family genes in BC, the correlations between histone family genes expression and clinical characteristics were investigated through data collected from TCGA. Therefore, the present study indicates that histone gene sets may be used as prognostic factors for survival prediction for BC patients.

Expression and potential prognostic value of histone family gene signature in breast cancer