Dataset Information

Bioinformatics Analysis of Expression and Alterations of BARD1 in Breast Cancer.

ABSTRACT: BACKGROUND:Breast cancer is one of the most common malignant tumor type in women worldwide. BARD1 could impact function of BRCA1 as its interaction partner. In the current study, we aimed to investigate the prognostic role of BARD1 expression as well as its alterations in breast cancer using different online tools. METHODS:We performed a bioinformatics analysis for BARD1 in patients with breast cancer using several online databases, including Oncomine, bc-GenExMiner, PrognoScan, Search Tool for the Retrieval of Interacting Genes, Cytoscape, and cBioPortal. RESULTS:We found that BARD1 was highly expressed in basal-like, HER2-E, and luminal B compared with normal-like subtype. Forest plot showed that BARD1 overexpression was correlated with worse distant metastasis-free survival (hazard ratio: 2.72, 95% confidence interval: 1.02-2.21; P = .0448), disease-specific survival (hazard ratio: 2.65, 95% confidence interval: 1.37-5.12; P = .0037), and disease-free survival (hazard ratio: 1.98, 95% confidence interval: 1.22-3.24; P = .0062) but positively correlated with overall survival (hazard ratio: 0.66, 95% confidence interval: 0.50-0.85; P = .0017). Multivariate analysis indicated that BARD1 expression was significantly associated with distant metastasis-free survival (hazard ratio: 4.60, 95% confidence interval: 1.22-17.28; P = .0239) whereas marginally significant for disease-free survival (hazard ratio: 1.00, 95% confidence interval: 1.00-1.01, P = .0630) and disease-specific survival (hazard ratio: 1.96, 95% confidence interval: 0.97-3.96; P = .0602). Meanwhile, alterations in BARD1 interaction network were associated with worse overall survival instead of BARD1 alteration alone. CONCLUSIONS:Bioinformatics analysis revealed that BARD1 may be a predictive biomarker for prognosis of breast cancer. However, future research is required to validate our findings.

SUBMITTER: Chen YZ

PROVIDER: S-EPMC6900616 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Bioinformatics Analysis of Expression and Alterations of BARD1 in Breast Cancer.

Chen Yong-Zi YZ Zuo Duo D Ren Hai-Ling HL Fan Sai-Jun SJ Ying Guoguang G

Technology in cancer research & treatment 20190101

<h4>Background</h4>Breast cancer is one of the most common malignant tumor type in women worldwide. BARD1 could impact function of BRCA1 as its interaction partner. In the current study, we aimed to investigate the prognostic role of BARD1 expression as well as its alterations in breast cancer using different online tools.<h4>Methods</h4>We performed a bioinformatics analysis for BARD1 in patients with breast cancer using several online databases, including Oncomine, bc-GenExMiner, PrognoScan, S ...[more]

PMID: 31808361

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Project description:BackgroundBreast cancer (BC) is the leading malignancy among women worldwide.AimThis work aimed to present a comprehensively bioinformatic analysis of gene expression profiles and to identify the hub genes during BC tumorigenesis, providing potential biomarkers and targets for the diagnosis and therapy of BC.Materials & methodsIn this study, multiple public databases, bioinformatics approaches, and online analytical tools were employed and the real-time reverse transcription polymerase chain reaction was implemented.ResultsFirst, we identified 10, 107, and 3869 differentially expressed genes (DEGs) from three gene expression datasets (GSE9574, GSE15852, and GSE42568, covering normal, para-cancerous, and BC samples, respectively), and investigated different biological functions and pathways involved. Then, we screened out 8, 16, and 29 module genes from these DEGs, respectively. Next, 10 candidate genes were determined through expression and survival analyses. We noted that seven candidate genes JUN, FOS, FOSB, EGR1, ZFP36, CFD, and PPARG were downregulated in BC compared to normal tissues and lower expressed in aggressive types of BC (basal, HER2+ , and luminal B), TP53 mutation group, younger patients, higher stage BC, and lymph node metastasis BC, while CD27, PSMB9, and SELL were upregulated. The present study discovered that the expression levels of these candidate genes were correlated with the infiltration of immune cells (CD8+ T cell, macrophage, natural killer [NK] cell, and cancer-associated fibroblast) in BC, as well as biomarkers of immune cells and immune checkpoints. We also revealed that promoter methylation, amplification, and deep deletion might contribute to the abnormal expressions of candidate genes. Moreover, we illustrated downstream-targeted genes of JUN, FOS, FOSB, EGR1, and ZFP36 and demonstrated that these targeted genes were involved in "positive regulation of cell death", "pathways in cancer", "PI3K-Akt signaling pathway", and so on.Discussion & conclusionWe presented differential gene expression profiles among normal, para-cancerous, and BC tissues and further identified candidate genes that might contribute to tumorigenesis and progression of BC, as potential diagnostic and prognostic targets for BC patients.

Project description:BackgroundMost, if not all, of the cellular functions of the BRCA1 protein are mediated through heterodimeric complexes composed of BRCA1 and a related protein, BARD1. Some breast-cancer-associated BRCA1 missense mutations disrupt the function of the BRCA1/BARD1 complex. It is therefore pertinent to determine whether variants of BARD1 confer susceptibility to breast cancer. Recently, a missense BARD1 variant, Cys557Ser, was reported to be at increased frequencies in breast cancer families. We investigated the role of the BARD1 Cys557Ser variant in a population-based cohort of 1,090 Icelandic patients with invasive breast cancer and 703 controls. We then used a computerized genealogy of the Icelandic population to study the relationships between the Cys557Ser variant and familial clustering of breast cancer.Methods and findingsThe Cys557Ser allele was present at a frequency of 0.028 in patients with invasive breast cancer and 0.016 in controls (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.11-3.01, p = 0.014). The alleleic frequency was 0.037 in a high-predisposition group of cases defined by having a family history of breast cancer, early onset of breast cancer, or multiple primary breast cancers (OR = 2.41, 95% CI 1.22-4.75, p = 0.015). Carriers of the common Icelandic BRCA2 999del5 mutation were found to have their risk of breast cancer further increased if they also carried the BARD1 variant: the frequency of the BARD1 variant allele was 0.047 (OR = 3.11, 95% CI 1.16-8.40, p = 0.046) in 999del5 carriers with breast cancer. This suggests that the lifetime probability of a BARD1 Cys557Ser/BRCA2 999del5 double carrier developing breast cancer could approach certainty. Cys557Ser carriers, with or without the BRCA2 mutation, had an increased risk of subsequent primary breast tumors after the first breast cancer diagnosis compared to non-carriers. Lobular and medullary breast carcinomas were overrepresented amongst Cys557Ser carriers. We found that an excess of ancestors of contemporary carriers lived in a single county in the southeast of Iceland and that all carriers shared a SNP haplotype, which is suggestive of a founder event. Cys557Ser was found on the same SNP haplotype background in the HapMap Project CEPH sample of Utah residents.ConclusionsOur findings suggest that BARD1 Cys557Ser is an ancient variant that confers risk of single and multiple primary breast cancers, and this risk extends to carriers of the BRCA2 999del5 mutation.

Project description:BackgroundMetaplastic 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.MethodsDifferentially 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.ResultsKLK5 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.ConclusionOur research indicated that KLK5 may be a pivotal molecule with a key role in the mechanism of tumorigenesis in metaplastic TNBC.

Project description:ObjectiveWe aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC).MethodsKaplan-Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan-Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC.ResultsORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration.ConclusionORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.

Dataset Information

Bioinformatics Analysis of Expression and Alterations of BARD1 in Breast Cancer.

Publications

Bioinformatics Analysis of Expression and Alterations of BARD1 in Breast Cancer.

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