Dataset Information

Potential Diagnostic and Prognostic Utility of miR-141, miR-181b1, and miR-23b in Breast Cancer.

ABSTRACT: miRNAs, a group of short noncoding RNAs, are key regulators of fundamental cellular processes and signaling pathways. Dysregulation of miRNA expression with known oncogenic or tumor suppressor functions has been associated with neoplastic transformation. Numerous studies have reported dysregulation of miRNA-141, miR-181b1, and miR-23b in a wide range of malignancies, including breast cancer. To the best of our knowledge, no previous study had demonstrated the expression of miR-141-3p, miR-181b1-5p, and miR-23b-3p in different histological grades and molecular subtypes of breast cancer. Here, we identified differential expression of these three miRNAs in breast cancer tissues compared with benign breast fibroadenomas. In addition, high expression levels of miR-141-3p and miR-181b1-5p are strongly associated with aggressive breast carcinomas. We also confirmed the clinical potential of using the three miRNAs individually or combined as diagnostic and prognostic markers in breast cancer. Using bioinformatics analyses, we identified 23 hub genes of these three miRNAs which are involved in key signaling pathways in breast cancer. Furthermore, the KM plotter online database analysis demonstrates the association between elevated expression of miR-141 and miR-181b and shorter overall survival of breast cancer patients. Together, our data suggest an oncogenic role of the studied miRNAs and highlight their molecular roles and potential clinical applications in breast cancer.

SUBMITTER: Taha M

PROVIDER: S-EPMC7697480 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Potential Diagnostic and Prognostic Utility of miR-141, miR-181b1, and miR-23b in Breast Cancer.

Taha Mohamed M Mitwally Noha N Soliman Ayman S AS Yousef Einas E

International journal of molecular sciences 20201114 22

miRNAs, a group of short noncoding RNAs, are key regulators of fundamental cellular processes and signaling pathways. Dysregulation of miRNA expression with known oncogenic or tumor suppressor functions has been associated with neoplastic transformation. Numerous studies have reported dysregulation of miRNA-141, miR-181b1, and miR-23b in a wide range of malignancies, including breast cancer. To the best of our knowledge, no previous study had demonstrated the expression of miR-141-3p, miR-181b1- ...[more]

PMID: 33202602

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Project description:Breast cancer is the most frequently diagnosed cancer globally and is one of the most important contributors to cancer-related deaths. Earlier diagnosis is known to reduce mortality, and better biomarkers are needed. MiRNA clusters often co-express and target mRNAs in a coordinated fashion, perturbing entire pathways; they thus merit further exploration for diagnostic or prognostic use. MiR-379/656, at chromosome 14q32, is the second largest miRNA cluster in the human genome and implicated in various malignancies including glioblastoma, melanoma, gastrointestinal tumors and ovarian cancer highlighting its potential importance. In this study, we focus on the diagnostic and prognostic potentials of MiR-379/656 in breast cancer and its molecular subtypes. We analyzed miRNA and mRNA next generation sequencing data from 903 primary tumors and 90 normal controls (source: The Cancer Genome Atlas). The differential expression profile between tumor and normal was analyzed using DeSEQ2. Penalized logistic regression modelling (lasso regression) was used to assess the predictive potential of MiR-379/656 expression for tumor and normal samples. The association between MiR-379/656 expression and overall patient survival was studied using Cox Proportional-Hazard Model. The target mRNAs (validated) of MiR-379/656 were annotated via pathway enrichment analysis to understand the biological significance of the cluster in breast cancer. The differential expression analysis for 1390 miRNAs (miRnome) revealed 310 upregulated (22.3%) and 176 downregulated (12.66%) miRNAs in breast cancer patients compared with controls. For MiR-379/656, 32 miRNAs (32/42; 76%) were downregulated. The MiR-379/656 cluster was found to be the most differentially expressed cluster in the human genome (p < 10-30). The Basal and Luminal B subtypes showed at least 83% (35/42) of the miRNAs to be downregulated. The binomial model prioritized 15 miRNAs, which distinguished breast cancer patients from controls with 99.15 ± 0.58% sensitivity and 77.78 ± 5.24% specificity. Overall, the Basal and Luminal B showed the most effective predictive power with respect to the 15 prioritized miRNAs at MiR-379/656 cluster. The decreased expression of MiR-379/656 was found to be associated with poorer clinical outcome in Basal and Luminal B subtypes, increasing tumor stage and tumor size/extent, and overall patient survival. Pathway enrichment for the validated targets of MiR-379/656 was significant for cancer-related pathways, especially DNA repair, transcriptional regulation by p53 and cell cycle checkpoints (adjusted p-value < 0.05). Genome informatics analysis of high throughput data for MiR-379/656 cluster has shown that a subset of 15 miRNAs from MiR-379/656 cluster can be used for the diagnostic and prognostic purpose of breast cancer and its subtypes-especially in Basal and Luminal B.

Project description:Expression of miR-34c and miR-141 in serum of colon cancer patients and their association with clinicopathological features and diagnostic value for colon cancer were investigated. A total of 64 patients with colon cancer admitted to Hubei Cancer Hospital from January 2016 to March 2018 were included in the experimental group, and 64 healthy subjects undergoing physical examination during the same period were the control group. The expression of miR-34c and miR-141 in serum of patients in the two groups were detected by RT-qPCR, and the association of miR-34c and miR-141 with the clinicopathological characteristics of colon cancer patients was analyzed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of miR-34c and miR-141 in colon cancer. The expression of miR-141 in serum of patients in the experimental group was significantly higher than that in the control group (P<0.05). Expression of miR-34c in serum of patients in the experimental group was significantly lower than that in the control group (P<0.05) and the expression of miR-34c and miR-141 in serum of the experimental group were associated with tumor diameter, clinical stage, degree of differentiation and lymph node metastasis (P<0.05). AUC of serum miR-34c in the diagnosis of colon cancer was 0.857 (95% CI: 0.795-0.919), with the cut-off value of 0.800, the diagnostic sensitivity of 84.38%, and the specificity of 68.75% and AUC of serum miR-141 in the diagnosis of colon cancer was 0.876 (95% CI: 0.810-0.941), with the cut-off value of 0.282, the diagnostic sensitivity of 70.31%, and the specificity of 96.88%. The ROC curve for the diagnosis of colon cancer was further plotted in combination with serum miR-34c and miR-141. AUC of the two combined for the diagnosis of colon cancer was 0.929 (95% CI: 0.884-0.974), with the cut-off value of 0.566, the diagnostic sensitivity of 84.38%, and the specificity of 93.75%. In conclusion, miR-34c and miR-141 might be involved in the occurrence and progression of colon cancer and could be used as biological indicators for early diagnosis of colon cancer.

Dataset Information

Potential Diagnostic and Prognostic Utility of miR-141, miR-181b1, and miR-23b in Breast Cancer.

Publications

Potential Diagnostic and Prognostic Utility of miR-141, miR-181b1, and miR-23b in Breast Cancer.

Similar Datasets

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