Prognostic and biological significance of microRNA-127 expression in human breast cancer.
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ABSTRACT:
SUBMITTER: Wang S
PROVIDER: S-EPMC4244930 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Breast cancer is a common malignant tumor, which severely threatens the health of women with an increasing incidence in many countries. Here, we identified C10orf10 as a novel differentially expression gene using expression microarray screening. The expression analysis indicated that C10orf10 was frequently decreased in human breast cancers compared to noncancerous breast tissues (81/95, P = 0.0063). Kaplan-Meier analysis indicated that patients with low C10orf10 expression showed a poorer prognosis both in mRNA (n = 1115, P = 0.0013) and protein (n = 100, P = 0.003) levels. Univariate and multivariate analysis showed that the C10orf10 expression was an independent prognostic factor for overall survival of breast cancer patients. Further analysis revealed that low expression of C10orf10 was an unfavorable factor for the prognosis of the patients who were luminal A, luminal B, Her2+ subtypes, at histological grade 2, lymph node negative and ER positive. Our data provided the first evidence that C10orf10 expression was frequently decreased in breast cancer tissues, and low expression of C10orf10 may be an important prognostic factor for poorer survival time of breast cancer patients.
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Project description:BACKGROUND: Dicer, an RNase III-type endonuclease, is the key enzyme involved in RNA interference and microRNA pathways. Aberrant expression of Dicer is reported in several human cancers. Our aim was to assess the prognostic role of Dicer in breast cancer. METHODS: The entire series comprised 666 invasive breast cancers (IBCs), 480 DCIS cases (397 associated with IBC and 83 pure DCIS) and 305 lymph node metastases. Cytoplasmic Dicer expression by immunohistochemistry was scored as negative (no staining) and positive (weak, moderate or strong staining). RESULTS: Dicer staining was assessable in 446 IBC, 128 DCIS and 101 lymph node metastases. Expression of Dicer was observed in 33% (145/446) of IBCs, 34% (44/128) of DCIS and 57% (58/101) of lymph node metastases. Dicer expression was increased in nodal metastases compared to primary tumours (p<0.001); and was associated with ER negativity (p<0.001), HER2 positivity (p<0.001), high Ki67 labeling index (p<0.001) and expression of basal-like biomarkers (p = 0.002). Dicer positivity was more frequent in the HER2 overexpressing (p<0.001) and basal-like (p = 0.002) subtypes compared to luminal A subtype. Dicer expression was associated with reduced overall survival (OS) on univariate analysis (p = 0.058) and remained an independent predictor of OS on multivariate analysis (HR 2.84, 95% CI 1.43-5.62, p = 0.003), with nodal status (HR 2.61, 95% CI 1.18-5.80, p = 0.018) and PR (HR 0.28, 95% CI 0.13-0.59, p = 0.001). Further, moderate or strong expression of Dicer was associated with improved disease-free survival in the HER2-overexpressing subtype compared to negative or weak expression (p = 0.038). CONCLUSION: Deregulated Dicer expression is associated with aggressive tumour characteristics and is an independent prognostic factor for OS. Our findings suggest that Dicer is an important prognostic marker in breast cancer and that its prognostic role may be subtype specific.
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Project description:PurposeThe aim of this study was to explore potential gene therapy targets for triple-negative breast cancer (TNBC).Patients and methodsThree gene expression profiles (GSE64790, GSE62931, and GSE38959) from the Gene Expression Omnibus (GEO) database were analyzed. The GEO2R analysis tool was used to screen for differentially expressed genes (DEGs) between TNBC and normal tissues, followed by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEGs. The protein-protein interaction network of DEGs was visualized using Metascape to identify the core genes. Subsequently, transcriptional data for the core genes in patients with breast cancer were investigated in the ONCOMINE database. Kaplan-Meier survival analysis was used to evaluate the prognostic value of core gene expression levels in patients with TNBC. Finally, the clinicopathological and long-term follow-up data of 39 patients with TNBC were retrospectively analyzed at the First Affiliated Hospital of the Bengbu Medical College between January 2014 and July 2020. Immunohistochemistry was used to evaluate the expression and subcellular localization of CCNB2 in TNBC tissues.ResultsA total of 66 DEGs were identified between TNBC and normal tissues, including 33 upregulated and 33 downregulated genes in TNBC. Furthermore, a potential protein complex was identified for five core genes. The high expression of these core genes, especially the overexpression of CCNB2, was correlated with a poor prognosis of patients with TNBC. The CCNB2 protein was expressed in the cytoplasm, and its expression was significantly higher in TNBC tissues than that in the adjacent nontumor tissues. Overall survival of patients was significantly correlated with the expression of CCNB2 (p < 0.05).ConclusionCCNB2 may play a crucial role in the development of TNBC and has the potential to be used as a prognostic biomarker for TNBC.
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Project description:BackgroundMicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types.MethodsWe evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n?=?150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ?7.0 were analyzed.ResultsThe relative expression of miR-10b in tumor as compared to its normal counterpart (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of patients with synchronous metastases (n?=?11, Median 0.25; IQR 0.11-1.02) as compared with patients without metastases (n?=?90, Median 0.09; IQR 0.04-0.29) (p?=?0.028). In the subgroup of patients without synchronous metastases (n?=?90), higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable (HR 1.16, p?=?0.021 and HR 1.20, p?=?0.015 respectively for 0.10 unitary increase of miR-10b RERs levels) and multivariable (HR1.30, p?<?0.001, and HR 1.31, p?=?0.003 respectively for 0.10 unitary increase of miR-10b RERs levels) Cox regression models. The addition of miR-10b RERs to the Nottingham Prognostic Index (NPI) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months. Survival C-indices significantly increased from 0.849 to 0.889 (p?=?0.009) for OS and from 0.735 to 0.767 (p?=?0.050) for DFS.ConclusionsOur results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients.
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