MicroRNA expression profiling analysis on a group of 52 heredo-familial and sporadic breast cancer samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Crippa Elisabetta
PROVIDER: S-ECPF-GEOD-46966 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:In this study, using microarray technology we did a transcriptome profiling of miRNAs on a group of 52 cases of familial (BRCA1- or BRCA2-mutated, or BRCAX, i.e. familial cases with no mutations in BRCA1 or BRCA2 genes) and sporadic breast cancers. Class comparison of different clinical characteristics of the samples identified miR-342 as the miRNA with the most significant association with estrogen receptor (ER) status (categorised as positive and negative) of the samples analysed. As ER is one of the bio-pathological features currently used in routine clinical practice to aid treatment decision in breast cancer, identification of this miRNA has been promising for finding new mechanisms involved in this tumour type as we had next demonstrated in a cellular model of breast cancer.
2014-05-14 | GSE46966 | GEO
Project description:In this study, using microarray technology we did a transcriptome profiling of miRNAs on a group of 52 cases of familial (BRCA1- or BRCA2-mutated, or BRCAX, i.e. familial cases with no mutations in BRCA1 or BRCA2 genes) and sporadic breast cancers. Class comparison of different clinical characteristics of the samples identified miR-342 as the miRNA with the most significant association with estrogen receptor (ER) status (categorised as positive and negative) of the samples analysed. As ER is one of the bio-pathological features currently used in routine clinical practice to aid treatment decision in breast cancer, identification of this miRNA has been promising for finding new mechanisms involved in this tumour type as we had next demonstrated in a cellular model of breast cancer. In the study presented here, microRNAs expression profiling on a well defined cohort of 52 breast cancer cases, followed up for more than 5 years, was used for a class comparison analysis with some relevant clinical characteristics of this tumour type like estrogen, progesterone or epidermal growth factor 2 receptor status.
2014-05-14 | E-GEOD-46966 | biostudies-arrayexpress
Project description:BackgroundGender-associated epigenetic alterations are poorly investigated in male and female familial breast cancer (fBC). MicroRNAs may contribute to the different biology in men and women particularly related to RASSF1A pathways.MethodsMicroarray technology was used to evaluate miRNA profile in 24 male and 43 female fBC. Key results were validated using RT-qPCR in an external samples set. In vitro studies were carried out to verify microRNA-target gene interaction.ResultsPathway enrichment analysis with the 287 differentially expressed microRNAs revealed several signalling pathways differently regulated in male and female cases. Because we previously hypothesised a peculiar involvement of RASSF1A in male fBC pathogenesis, we focussed on the MAPK and the Hippo signalling pathways that are regulated by RASSF1A. Male miR-152 and miR-497 upregulation and RASSF1A and NORE1A interacting gene downregulation were observed, confirming a possible indirect interaction between miRNAs and the two genes.ConclusionsFor the first time, a different microRNA expression pattern in male and female fBC has been shown. Moreover, the importance of RASSF1A pathway in male fBC carcinogenesis has been confirmed, highlighting a possible role for miR-152 and miR-497 in controlling MAPK and Hippo signalling pathways, regulated by RASSF1A.
| S-EPMC4264445 | biostudies-literature
Project description:BackgroundThe role of miRNAs in familial breast cancer (fBC) is poorly investigated as also in the BRCA-like tumors. To identify a specific miRNA expression pattern which could allow a better fBC classification not only based on clinico-pathological and immunophenotypical parameters we analyzed miRNA profile in familial and sporadic samples. Moreover since BRCA1 tumors and sporadic triple negative (TN) breast tumors share similarities regarding clinical outcomes and some histological characteristics, we focused on TN and not TN cases.MethodsThe sample set included fresh frozen tissue samples, including 39 female fBCs (19 BRCA-related and 20 BRCAX) and 12 male fBC (BRCAX). Moreover, we considered TN and non TN (NTN), 21 BRCA-related and 27 sporadic BCs. MiRNA profiling was performed through GeneChip miRNA v.1.0 Array (Affymetrix). ANOVA, hierarchical and consensus clustering analyses allowed identification of pattern of expression of miRNAs and pathway enrichment analysis, considering validated target genes, was carried out to achieve a deeper biological understanding.ResultsANOVA test led to the identification of 53 deregulated miRNAs; hierarchical and consensus clustering of female fBCs (fFBCs) and male fBCs (fMBCs) highlighted the presence of 3 sample clusters named FBC1, FBC2 and FBC3. We found a correlation between ER-status and the three sample clusters. The three clusters are distinct by a different expression of two clusters of miRNAs (CLU1 and CLU2), which resulted to be different in targeted pathways. In particular, CLU1 targets cellular pathways and CLU2 is involved in epigenetic activities. Considering TN and NTN BRCA-related and sporadic tumors, a hierarchical clustering identified two clusters of miRNAs, which were not so different from CLU1 and CLU2, both in miRNA content and targeted pathways.ConclusionsOur results highlighted the importance of miRNA regulation to better clarify similarities and differences between familial and sporadic BC groups.
| S-EPMC4239401 | biostudies-literature
Project description:RationaleIdiopathic interstitial pneumonia (IIP) and its familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms. Both the genetics and the histologic type of IIP play a role in the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these subtypes are unknown.ObjectivesTo evaluate gene expression in the lung tissue of patients with usual interstitial pneumonia or nonspecific interstitial pneumonia that was either familial or nonfamilial in origin, and to compare it with gene expression in normal lung parenchyma.MethodsWe profiled RNA from the lungs of 16 patients with sporadic IIP, 10 with familial IIP, and 9 normal control subjects on a whole human genome oligonucleotide microarray.ResultsSignificant transcriptional differences exist in familial and sporadic IIPs. The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish IIP from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway. The role of the chemokine CXCL12 in disease pathogenesis was confirmed in the murine bleomycin model of lung injury, with C57BL/6(CXCR4+/-) mice demonstrating significantly less collagen deposition than C57BL/6(CXCR4+/+) mice. Whereas substantial differences exist between familial and sporadic IIPs, we identified only minor gene expression changes between usual interstitial pneumonia and nonspecific interstitial pneumonia.ConclusionsTaken together, our findings indicate that differences in gene expression profiles between familial and sporadic IIPs may provide clues to the etiology and pathogenesis of IIP.
| S-EPMC1899261 | biostudies-literature
Project description:BackgroundWhile a number of studies have examined miRNA profiles across the molecular subtypes of breast cancer, it is unclear whether BRCA1 basal-like cancers have a specific miRNA profile. This study aims to compare grade independent miRNA expression in luminal cancers, sporadic and BRCA1 basal-type breast cancers. It also aims to ascertain an immunohistochemical profile regulated by BRCA1 specific miRNAs for potential diagnostic use.MethodsmiRNA expression was assessed in 11 BRCA1 basal, 16 sporadic basal, 17 luminal grade 3 cancers via microarrays. The expression of Cyclin D1, FOXP1, FIH-1, pan-ERβ, NRP1 and CD99, predicted to be regulated by BRCA1 specific miRNAs by computer prediction algorithms, was assessed via immunohistochemistry in a cohort of 35 BRCA1 and 52 sporadic basal-like cancers. Assessment of cyclin D1, FOXP1, NRP1 and CD99 expression was repeated on a validation cohort of 82 BRCA1 and 65 sporadic basal-like breast cancers.ResultsUnsupervised clustering of basal cancers resulted in a "sporadic" cluster of 11 cancers, and a "BRCA1" cluster of 16 cancers, including a subgroup composed entirely of 10 BRCA1 cancers. Compared with sporadic basal cancers, BRCA1 cancers showed reduced positivity for proteins predicted to be regulated by miRNAs: FOXP1 (6/20[30 %] vs. 37/49[76 %], p < 0.001), cyclin D1 (8/22[36 %] vs. 30/46[65 %], p = 0.025), NRP1 (2/20[10 %] vs. 23/46[50 %], p = 0.002). This was confirmed in the validation cohort (all p < 0.001). Negative staining for 2 or more out of FOXP1, cyclin D1 and NRP1 predicts germline BRCA1 mutation with a sensitivity of 92 %, specificity of 44 %, positive predictive value of 38 % and a negative predictive value of 94 %.ConclusionSporadic and BRCA1 basal-like cancers have grade independent miRNA expression profiles. Furthermore miRNA driven differences in the expression of proteins in BRCA1 basal cancers may be detected via immunohistochemistry. These findings may have important diagnostic implications, as immunohistochemical assessment of basal cancers, in addition to the patient's family and clinical history, may potentially identify patients who may benefit from BRCA1 gene testing.
| S-EPMC4494690 | biostudies-literature
Project description:Analysis of miRNA expression in grade 3 luminal, sporadic and BRCA1 associated basal-like breast cancers 44 primary grade III breast cancer (11 BRCA1 basal, 16 sporadic basal, 17 luminal) and 13 normal breast FFPE (formalin fixed, paraffin embedded) specimens, plus 7 controls and 5 cell lines were analysed. The aim of the study was to derive grade-specific miRNA signatures for sporadic and BRCA1 basal-like breast cancers, and to ascertain an immunohistochemical profile regulated by BRCA1 specific miRNAs for potential diagnostic uses.
| S-ECPF-GEOD-61438 | biostudies-other
Project description:Fanconi anemia group D2 protein (FANCD2) and breast cancer type 1 susceptibility protein (BRCA1), within the FA/BRCA pathway, are involved in the regulation of DNA damage repair, which is associated with breast cancer (BC) progression. The present study aimed to investigate BRCA1 and FANCD2 expression in breast cancer, and to highlight the association with patient clinical characteristics and prognoses. The BRCA1 and FANCD2 proteins were detected by immunohistochemistry in 335 tissue samples obtained from patients with BC, including 141 patients with familial BC (FBC), 147 patients with sporadic breast cancer (SBC) and 47 patients with benign breast tumors. Western blotting was used to detect the FANCD2 ubiquitination level in 56 frozen specimens that were randomly selected from the SBC group. Protein expression of BRCA1 in the FBC group was positively associated with tumor size, lymphatic invasion, Tumor-Node-Metastasis (TNM) stage, estrogen receptor (ER) status and FANCD2 expression. Protein expression of FANCD2 in the SBC group was positively associated with tumor size, TNM stage, ER status and Ki-67 index. Survival analyses revealed that BRCA1 expression was associated with the decreased disease-free survival (DFS) rate of patients with FBC (versus no BRCA1 expression) and that FANCD2 was associated with decreased DFS of patients with SBC (versus no FANCD expression). Univariable and multivariable analyses demonstrated that BRCA1 expression may be an independent prognostic factor in the FBC group. In the SBC group, FANCD2 high expression and low ubiquitination levels were considered as independent prognostic factors. In conclusion, the present study suggested that BRCA1 and FANCD2 expression, and FANCD2 ubiquitination levels, may be considered of novel potential prognostic value in patients with BC.
| S-EPMC6403512 | biostudies-literature
Project description:BackgroundPrimary macronodular adrenal hyperplasia (PMAH), previously termed ACTH-independent macronodular adrenal hyperplasia (AIMAH), is a rare cause of Cushing's syndrome usually characterized by functioning adrenal macronodules and increased cortisol production.MethodsTo screen and analyse the microRNA (miRNA) profile of PMAH in order to elucidate its possible pathogenesis, a miRNA microarray was used to test tissue samples from patients with familial PMAH, patients with sporadic PMAH and normal control samples of other nontumour adrenocortical tissues and identify characteristic microRNA expression signatures. Randomly selected miRNAs were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, the key signalling pathways and miRNAs involved in PMAH pathogenesis were determined by gene ontology and pathway analysis.ResultsCharacteristic microRNA expression signatures were identified for patients with familial PMAH (16 differentially expressed microRNAs) and patients with sporadic PMAH (8 differentially expressed microRNAs). The expression of the selected miRNAs was confirmed by qRT-PCR, suggesting the high reliability of the miRNA array analysis results. Pathway analysis showed that the most enriched pathway was the renal cell carcinoma pathway. Overexpression of miR-17, miR-20a and miR-130b may inhibit glucocorticoid-induced apoptosis in PMAH pathogenesis.ConclusionWe identified the miRNA signatures in patients with familial and sporadic PMAH. The differentially expressed miRNAs may be involved in the mechanisms of PMAH pathogenesis. Specific miRNAs, such as miR-17, miR-20a and miR-130b, may be new targets for further functional studies of PMAH.
| S-EPMC8729020 | biostudies-literature
Project description:IntroductionMicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. To test the hypothesis that there is a specific miRNA expression signature which characterizes male breast cancers, we performed miRNA microarray analysis in a series of male breast cancers and compared them with cases of male gynecomastia and female breast cancers.MethodsParaffin blocks were obtained at the Department of Pathology of Thomas Jefferson University from 28 male patients including 23 breast cancers and five cases of male gynecomastia, and from 10 female ductal breast carcinomas. The RNA harvested was hybridized to miRNA microarrays (~1,100 miRNA probes, including 326 human and 249 mouse miRNA genes, spotted in duplicate). To further support the microarray data, an immunohistochemical analysis for two specific miRNA gene targets (HOXD10 and VEGF) was performed in a small series of male breast carcinoma and gynecomastia samples.ResultsWe identified a male breast cancer miRNA signature composed of a large portion of underexpressed miRNAs. In particular, 17 miRNAs with increased expression and 26 miRNAs with decreased expression were identified in male breast cancer compared with gynecomastia. Among these miRNAs, some had well-characterized cancer development association and some showed a deregulation in cancer specimens similar to the one previously observed in the published signatures of female breast cancer. Comparing male with female breast cancer miRNA expression signatures, 17 significantly deregulated miRNAs were observed (four overexpressed and 13 underexpressed in male breast cancers). The HOXD10 and VEGF gene immunohistochemical expression significantly follows the corresponding miRNA deregulation.ConclusionsOur results suggest that specific miRNAs may be directly involved in male breast cancer development and that they may represent a novel diagnostic tool in the characterization of specific cancer gene targets.
| S-EPMC2750120 | biostudies-literature