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Predictive value of miR-9 as a potential biomarker for nasopharyngeal carcinoma metastasis.

ABSTRACT: BACKGROUND:Nasopharyngeal carcinoma (NPC) has a distinctive geographic distribution and is characterised by its strong tendency of metastasis. We aimed to examine the microRNA (miRNA) expression profiles in plasma samples of NPC patients to explore their clinical significance in disease development and progression. METHODS:This study was divided into four steps: (1) confirmation of differentially expressed miRNAs using microarray analysis and quantitative PCR validation; (2) comparison of plasma miR-9 levels during NPC progression; (3) evaluation of the predictive performance of plasma miR-9 as a biomarker for NPC metastasis; and (4) comparison of plasma miR-9 levels between pre- and post-treatment samples. RESULTS:Plasma microarray profiling identified 33 differentially expressed miRNAs between NPC patients and healthy volunteers. The significantly declined level of miR-9 in NPC patients was confirmed through two-stage validation. The low level of plasma miR-9 was significantly correlated with worse lymphatic invasion and advanced TNM stage. The plasma miR-9 could distinguish locoregional from metastatic NPC cases with a high sensitivity and specificity. Furthermore, the plasma miR-9 level was significantly elevated in post-treatment plasma compared with those pre-treatment samples. CONCLUSION:Our study reports that plasma miR-9 may serve as a useful biomarker to predict NPC metastasis and to monitor tumour dynamics.

SUBMITTER: Lu J

PROVIDER: S-EPMC3899774 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Predictive value of miR-9 as a potential biomarker for nasopharyngeal carcinoma metastasis.

Lu J J Xu X X Liu X X Peng Y Y Zhang B B Wang L L Luo H H Peng X X Li G G Tian W W He M M He M M Li X X

British journal of cancer 20131210 2

<h4>Background</h4>Nasopharyngeal carcinoma (NPC) has a distinctive geographic distribution and is characterised by its strong tendency of metastasis. We aimed to examine the microRNA (miRNA) expression profiles in plasma samples of NPC patients to explore their clinical significance in disease development and progression.<h4>Methods</h4>This study was divided into four steps: (1) confirmation of differentially expressed miRNAs using microarray analysis and quantitative PCR validation; (2) compa ...[more]

PMID: 24327016

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Project description:ObjectivesTo determine the predictive value of pretreatment MRI texture analysis for progression-free survival (PFS) in patients with primary nasopharyngeal carcinoma (NPC).MethodsEthical approval by the institutional review board was obtained for this retrospective analysis. In 79 patients with primary NPC, texture analysis of the primary tumour was performed on pretreatment T2 and contrast-enhanced T1-weighted images (T2WIs and CE-T1WIs). The Cox proportional hazards model was used to determine the association of texture features, tumour volume and the tumour-node-metastasis (TNM) stage with PFS. Survival curves were plotted using the Kaplan-Meier method. The prognostic performance was evaluated with the receiver operating characteristic (ROC) analyses and C-index.ResultsTumour volume (hazard ratio, 1.054; 95% confidence interval [CI], 1.016-1.093) and CE-T1WI-based uniformity (hazard ratio, 0; 95% CI, 0-0.001) were identified as independent predictors for PFS (p < 0.05). Kaplan-Meier analysis showed that smaller tumour volume (less than the cut-off value, 11.699 cm3) and higher CE-T1WI-based uniformity (greater than the cut-off value, 0.856) were associated with improved PFS (p < 0.05). The combination of CE-T1WI-based uniformity with tumour volume and the overall stage predicted PFS better (area under the curve [AUC], 0.825; Cindex, 0.794) than the tumour volume (AUC, 0.659; C-index, 0.616) or the overall stage (AUC, 0.636; C-index, 0.627) did (p < 0.05).ConclusionsA texture parameter of pretreatment CE-T1WI-based uniformity improves the prediction of PFS in NPC patients.Key points• Higher CE-T1WI-based uniformity and smaller tumour volume are predictive of improved PFS in NPC patients. • The combination of CE-T1WI-based uniformity with tumour volume and the overall stage has a better predictive ability for PFS than the tumour volume or the overall stage alone. • Pretreatment MRI texture analysis has a prognostic value for NPC patients.

Project description:BACKGROUND:The molecular mechanisms underlying dysregulation of microRNAs have been documented in nasopharyngeal carcinoma (NPC). Our previous study demonstrated that plasma miR-124 was down-regulated in NPC using microarray analysis and quantitative PCR validation. Though growing studies showed that down-regulated miR-124 was closely related to tumourigenesis in various types of cancers, the role of miR-124 in NPC remains largely unknown. METHODS:The expression level of miR-124 was evaluated in NPC cell lines and patient specimens using quantitative reverse transcription-PCR (Real-time qPCR). The clinicopathological significance of the resultant data was later analyzed. Then, we explored the role of miR-124 in NPC tumorigenesis by in vitro and in vivo experiments. Homo sapiens forkhead box Q1 (Foxq1) was confirmed as a novel direct target gene of miR-124 by the dual-luciferase assay and western bolt. RESULTS:We found that miR-124 was commonly down-regulated in NPC specimens and NPC cell lines. The expression of miR-124 was inversely correlation with clinical stages and marked on T stages. Then, the ectopic expression of miR-124 dramatically inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Furthermore, we identified Foxq1 as a novel direct target of miR-124. Functional studies showed that knockdown of Foxq1 inhibited cell growth, migration and invasion, whereas Foxq1 overexpression partially rescued the suppressive effect of miR-124 in NPC. In clinical specimens, Foxq1 was commonly up-regulated in NPC, and the level increased with clinical stages and T stages. Additionally, the level of Foxq1 was inversely correlated with miR-124. CONCLUSIONS:Our results demonstrate that miR-124 functions as a tumor-suppressive microRNA in NPC, and that its suppressive effects are mediated chiefly by repressing Foxq1 expression. MiR-124 could serve as an independent biomarker to identify patients with different clinical characteristics. Therefore, our findings provide valuable clues toward the understanding the of mechanisms of NPC pathogenesis and provide an opportunity to develop new effective clinical therapies in the future.

Project description:BACKGROUND: Mitochondrial proteomic alterations of nasopharyngeal carcinoma metastasis remain unknown. Our purpose is to screen mitochondrial proteins for the elucidation of the molecular mechanisms of nasopharyngeal carcinoma metastasis and the discovery of metastasis-related biomarkers. METHODS: Mitochondria were isolated from nasopharyngeal carcinoma metastatic (5-8F) and nonmetastatic (6-10B) cell lines, respectively. After characterization of isolated mitochondria, mitochondrial differentially expressed proteins (DEPs) were quantified by two-dimensional difference in-gel electrophoresis (2D-DIGE), and identified by peptide mass fingerprint (PMF) and tandem mass spectrometry (MS/MS). A functional enrichment analysis and a protein-protein interaction sub-network analysis for DEPs were carried out with bioinformatics. Furthermore, siRNAs transient transfections were used to suppress expressions of some up-regulated DEPs in metastatic cells (5-8F), followed by Transwell Migration assay. RESULTS: Sixteen mitochondrial DEPs including PRDX3 and SOD2 were identified. Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential. The functional enrichment analyses of DEPs discovered five significant biological processes including cellular response to reactive oxygen species, hydrogen peroxide metabolic process, regulation of mitochondrial membrane potential, cell redox homeostasis and oxidation reduction, and five significant molecular functions including oxidoreductase activity, caspase inhibitor activity, peroxiredoxin activity, porin activity and antioxidant activity. A protein-protein interaction sub-network of DEPs was generated with literature data. Ten mitochondrial DEPs including PRDX3, PRDX6, SOD2, ECH1, SERPINB5, COX5A, PDIA5, EIF5A, IDH3B, and PSMC4 were rationalized in the tumor-stroma co-evolution model that mitochondrial oxidative stress directly contributes to tumor metastasis. CONCLUSIONS: Sixteen mitochondrial DEPs were identified with mass spectrometry and ten of them were rationalized in the tumor-stroma co-evolution model. Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential. These data suggest that those mitochondrial DEPs are potential biomarkers for NPC metastasis, and their dysregulation would play important roles in mitochondria oxidative stress-mediated NPC metastatic process.

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Predictive value of miR-9 as a potential biomarker for nasopharyngeal carcinoma metastasis.

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Predictive value of miR-9 as a potential biomarker for nasopharyngeal carcinoma metastasis.

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