Distinctive microRNA expression in early stage nasopharyngeal carcinoma patients.
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ABSTRACT:
SUBMITTER: Li S
PROVIDER: S-EPMC5134390 | biostudies-other | 2016 Dec
REPOSITORIES: biostudies-other
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Project description:Radiation encephalopathy (RE) is one of the most severe complications in nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). However, the morphological alteration of early RE is insufficiently investigated. We aimed to investigate the cortical thickness and surface area alterations in NPC patients with or without RE in the follow-up. A total of 168 NPC patients each underwent a single scan and analysis at various times either Pre-RT (n = 56) or Post-RT (n = 112). We further divided the Post-RT NPC patients into three groups based on the time of the analysis following RT (Post-RTwithin 6 months and Post-RT7-12 months) or whether RE signs were detected in the analysis (Post-RTRE proved in follow-up). We confined the vertex-wise analyses of the cortical thickness and surface area to the bilateral temporal lobes. Interestingly, we revealed a gradual increase in the cortical surface area of the temporal lobe with increasing time after RT within the Post-RTRE proved in follow-up group, consistent with the between-group findings, which showed a significant increase in cortical surface area in the Post-RTRE proved in follow-up group relative to the Pre-RT group and the Post-RTwithin 6 months group. By contrast, such a trend was not observed in the cortical thickness findings. We concluded that the cortical surface area, rather than cortical thickness, may serve as a potential biomarker for early diagnosis of RE.
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Project description:Purpose: This study aims to develop liquid biopsy assays for early HCC diagnosis and prognosis. Methods: Twenty-three microRNAs were first consolidated as a panel (HCCseek-23 panel) based on their reported functions in HCC development. Serum samples were collected from 103 early-stage HCC patients before and after hepatectomy. Quantitative PCR and machine learning random forest models were applied to develop diagnostic and prognostic models. Results: For HCC diagnosis, HCCseek-23 panel demonstrated 81% sensitivity and 83% specificity for identifying HCC in the early-stage; it showed 93% sensitivity for identifying alpha-fetoprotein (AFP)-negative HCC. For HCC prognosis, the differential expressions of 8 microRNAs (HCCseek-8 panel: miR-145, miR-148a, miR-150, miR-221, miR-223, miR-23a, miR-374a, and miR-424) were significantly associated with disease-free survival (DFS) (Log-rank test p-value = 0.001). Further model improvement using these HCCseek-8 panel in combination with serum biomarkers (i.e. AFP, ALT, and AST) demonstrated a significant association with DFS (Log-rank p-value = 0.011 and Cox proportional hazards analyses p-value = 0.002). Conclusion: To the best of our knowledge, this is the first report to integrate circulating miRNAs, AST, ALT, AFP, and machine learning for predicting DFS in early HCC patients undergoing hepatectomy. In this setting, HCCSeek-23 panel is a promising circulating microRNA assay for diagnosis, while HCCSeek-8 panel is promising for prognosis to identify early HCC recurrence.
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Project description:Background/purposeNasopharyngeal carcinoma (NPC) is a malignant neoplasm of the head and neck. This study aims to use integrated bioinformatics technologies to develop a predictive miRNA-signature correlated with the prognosis of NPC.Materials and methodsInitially, the differentially expressed miRNAs (DEMs) in NPC were identified, and then DEMs related to the prognosis of NPC were further screened. Subsequently, the relatively important DEMs identified by random forest algorithm were used to construct a predictive signature by multivariate COX regression analysis. Moreover, PCA, Kaplan-Meier analysis, time-dependent ROC analysis, and univariate and multivariate COX regression analysis were performed to evaluate the ability of the signature in risk identification and prognosis prediction in NPC.ResultsHsa-miR-29c, hsa-miR-30e and hsa-miR-93 were selected from DEMs to construct a signature, and their abnormal expression was significantly associated with poor prognosis of NPC. The average AUC values of 1- to 5-year OS, DFS and DMFS predicted by the signature were all above 0.7, and showed better clinical independence than other indexes. In addition, 295 differentially expressed mRNAs could be used as potential target genes of the 3 DEMs. Among them, 56 differentially expressed mRNAs were related to PFS. GO and KEGG enrichment analysis indicated that the poor prognosis of NPC was related to the abnormality of chromosomes, cytokines, and chemokines.ConclusionWe constructed a three-miRNA signature with good independent performance in predicting the prognosis for NPC. This study may lay the foundation for exploring new therapeutic targets and improving survival outcomes in NPC patients.
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Project description:The extraocular muscles (EOMs) are a unique group of muscles that are anatomically and physiologically distinct from other muscles. We and others have shown that EOMs have a unique transcriptome and proteome. Here we investigated the expression pattern of microRNAs (miRNAs), as they may play a role in generating the unique EOM allotype. We isolated RNA and screened LC Sciences miRNA microarrays covering the sequences of miRBase 10.0 to define the microRNAome of normal mouse EOM and tibialis anterior (TA) limb muscle. Seventy-four miRNAs were found to be differentially regulated (P value <0.05) of which 31 (14 upregulated, 17 downregulated) were differentially regulated at signal strength >500. Muscle-specific miRNAs miR-206 and miR-499 were upregulated and miR-1, miR-133a, and miR-133b were downregulated in EOM. Quantitative PCR (qPCR) analysis was used to validate the differential expression. Bioinformatic tools were used to identify potential miRNA-mRNA-protein interactions and integrate data with previous transcriptome and proteomic profiling data. Luciferase assays using cotransfection of precursor miRNAs with reporter constructs containing the 3'-untranslated region of predicted target genes were used to validate targeting by identified miRNAs. The definition of the EOM microRNAome complements existing transcriptome and proteome data about the molecular makeup of EOM and provides further insight into regulation of muscle genes. These data will also help to further explain the unique EOM muscle allotype and its differential sensitivity to diseases such as Duchenne muscular dystrophy and may assist in development of therapeutic strategies.
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Project description:MicroRNAs (miRNAs) are a family of small non-coding RNA molecules of about 20-23 nucleotides in length, which negatively regulate protein-coding genes at post-transcriptional level. Using a stem-loop real-time-PCR method, we quantified the expression levels of 270 human miRNAs in 13 nasopharyngeal carcinoma (NPC) samples and 9 adjacent normal tissues, and identified 35 miRNAs whose expression levels were significantly altered in NPC samples. Several known oncogenic miRNAs, including miR-17-92 cluster and miR-155, are among the miRNAs upregulated in NPC. Tumour suppressive miRNAs, including miR-34 family, miR-143, and miR-145, are significantly downregulated in NPC. To explore the roles of these dysregulated miRNAs in the pathogenesis of NPC, a computational analysis was performed to predict the pathways collectively targeted by the 22 significantly downregulated miRNAs. Several biological pathways that are well characterised in cancer are significantly targeted by the downregulated miRNAs. These pathways include TGF-Wnt pathways, G1-S cell cycle progression, VEGF signalling pathway, apoptosis and survival pathways, and IP3 signalling pathways. Expression levels of several predicted target genes in G1-S progression and VEGF signalling pathways were elevated in NPC tissues and showed inverse correlation with the down-modulated miRNAs. These results indicate that these downregulated miRNAs coordinately regulate several oncogenic pathways in NPC.
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Project description:BackgroundEarly diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC.MethodsExosomes in plasma were extracted by ultra-high-speed centrifugation. Western blot and transmission electron microscopy (TEM) were used to verify the purity of exosomes. The sequencing data (6 plasma samples from healthy volunteers vs. 6 NPC plasma samples) were analyzed by principal component analysis (PCA), DESeq2, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and TargetScan. The differentially expressed miRNAs (DEmiRNAs) were obtained from the dataset (GSE118720) downloaded from the Gene Expression Omnibus (GEO) repository. Additionally, the datasets downloaded from the GEO database (GSE12452, GSE13597, GSE53819, GSE64634) were used to predict the target genes and functions of hsa-miR-1301-3p. qPCR was applied to verify the differences in the expressions of hsa-miR-1301-3p between 10 normal plasma and 10 NPC plasma samples.ResultsWestern blot, TEM, and Nanoparticle Tracking Analysis showed adequate purity of the extracted exosomes. RNA-seq analysis revealed 21 upregulated miRNAs, and 10 downregulated miRNAs in plasma exosomes of early-stage NPC patients. GO analysis showed that the target genes of DEmiRNAs were mainly enriched in DNA synthesis and transcription regulation. KEGG analysis revealed that DEmiRNAs were mainly enriched in PI3K-Akt and MAPK signaling pathways. Moreover, the expression of hsa-mir-1301-3p was verified to be significantly upregulated in enlarged samples of plasma exosomes.ConclusionsWe identified several DEmiRNAs extracted from tumor-derived exosomes between normal plasma and early-stage NPC plasma. Bioinformatics analyses indicated that these DEmiRNAs may be related to NPC development. Our study may provide novel insights into underlying biomarkers and mechanisms of plasma exosomes in early-stage NPC.
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Project description:BackgroundOral mucositis is the most common complication after radiotherapy of nasopharyngeal carcinoma (NPC). Previous studies had revealed that oral microbiota took great alteration soon after and during radiotherapy. Here, we aimed to investigate if the alteration of oral microbiota was related to delayed healing of oral mucositis after six month of radiotherapy.MethodsWe recruited 64 NPC patients and collected samples after six month of radiotherapy. 32 patients were included into normal healing group (N), 22 patients were mild delayed healing group (M), while 10 patients were severe delayed healing group (S). 16S rRNA gene sequencing was used to assess and identify oral microbiota alteration.ResultsThe diversity of oral microbial communities was not significantly different. Composition of oral microbial was huge different among S group, for the Actinobacteria and Veillonella were significantly increased, which showed significant dysbiosis of the oral microbiome. Functional analysis of metabolic pathways of oral microbiota demonstrated that degradation of organic acids and amino acids were significantly increased in S group. Moreover, phenotype analysis found that relative abundance of aerobic and biofilm formation were higher in S group. We also found the Actinobacteria co-occurred with Veillonellaceae, but anti-occurred with other biofilm oral bacteria. These two biomarkers may be predictable for severe delayed healing of oral mucositis after radiotherapy.ConclusionThis study suggests a potential association between oral microbiome and delayed healing of oral mucositis. The Actinobacteria and Veillonellaceae may be biomarkers in predicting the risks for the severe delayed healing of oral mucositis after radiotherapy of NPC.
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Project description:Background: Patients with nasopharyngeal carcinoma (NPC) frequently developed the problem of malnutrition at the time of diagnosis. Chemoradiotherapy (CRT) can even worsen the situation. Therefore, nutritional intervention should be applied to prevent CRT-associated weight loss and interruption of CRT. However, it is still controversial if early nutritional intervention is beneficial to NPC patients with CRT. This study is to investigate the influence of early nutritional intervention on advanced NPC patients with CRT by evaluating the nutritional status and CRT treatment tolerance. Methods: A cohort of 78 stage III-IV nasopharyngeal carcinoma patients was divided into early (n=46) and late (n=32) nutrition intervention groups. The early group of patients received nutritional support at the beginning of CRT, whereas the late group received such a support until development of the side effects, like 50% required oral dietary intake or >10% weight loss. The data were collected and statistically analyzed. Results: There was no significant difference in baseline clinical characteristics between these two groups, suggesting that no selection bias occurred. Both groups of patients had weight loss at the end of CRT and 3 months thereafter. However, at the later time point, the early group started to regain their weight, while the late group continued to lose weight. At both time points, the early group had a lower percentage of weight loss than the late group. Similar results were also obtained for BMI, albumin, and pre-albumin levels (All p<0.05). Besides, the early group showed a lower rate of advanced mucositis, a lower percentage of patients with more than 3 days RT breaks, fewer days of RT delayed for toxicity, and a lower percentage of patients with unplanned hospitalizations (All p<0.05). A linear correlation was also found between the percentage of weight loss and the number of days of RT delayed. Conclusion: Early nutritional intervention provides beneficial outcomes to NPC patients by maintaining their nutritional status and enhancing CRT treatment tolerance. Our results also indicated early nutrition intervention may reduce the hospital cost and improve patients' life quality.
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