Geometrically encoded SERS nanobarcodes for the logical detection of nasopharyngeal carcinoma-related progression biomarkers.
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ABSTRACT:
SUBMITTER: Lin D
PROVIDER: S-EPMC8173014 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nasopharyngeal carcinoma (NpC) is a malignant disease associated with Epstein-Barr virus infection, and often diagnosed at an advanced stage. This significantly curtails patient survival. We hypothesize that a panel of biomarkers can be assembled to assess NpC incidence, early detection, and tumor progression during therapeutic intervention. Our thesis rests on a model of successfully predicting high-risk gliomas by means of a carefully crafted panel of molecular mitotic biomarkers (i.e., securin, survivin and MCM2). The strategy we propose holds strong promise for prevention and cure of NpC. The approach we propose seeks to identify certain biomarkers from viral materials, patient tissues and assessment of related diseases, whose signatures, taken together, will be endowed with some degree of congruency, or sense of a coordinated language (i.e., "votes"). Biomarker "voting" will then permit to outline a broad coordinated molecular map for the molecular and epigenetic characterization of each individual patient's NpC tumor. We will draw on the process of contrasting biomarkers in health and disease, which rests on the auto-proteomic concept particularly relevant in high-risk cancer individuals, such as is the case for NpC. In brief we defend, current advances in human proteome profiling proffers the possibility of having individual baseline proteomic profiles using local body fluids (e.g., saliva, nasal secretions, sputum) or systemic fluids (e.g., plasma, serum, cerebrospinal fluid) to unravel a personalized molecular map for high-risk NpC individuals. Regular check-up will monitor for new or impending manifestations of NpC, and provide a secure assessment of incidence and early detection.
| S-EPMC2720668 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC) is an epithelial malignancy ubiquitously associated with Epstein-Barr virus (EBV). EBV generates various viral microRNAs (miRNAs) by processing the BHRF1 and BamHI A rightward (BART) transcripts. These BART miRNAs are abundantly expressed in NPC, but their functions and molecular mechanisms remain largely unknown. Our study found that the EBV-encoded microRNA BART-22 was significantly upregulated in NPC tissues and positively correlated with tumor progression. Furthermore, we found that EBV-miR-BART-22 was a significant predictor of poor prognosis in NPC. A reliable nomogram model to predict the preoperative overall survival (OS) of NPC patients was established. The area under the receiver operating characteristic (ROC) curve value for 5-year survival was 0.91. Elevated levels of EBV-miR-BART-22 significantly promoted the epithelial-mesenchymal transition (EMT) and metastasis of NPC cells in vivo and in vitro. We found that EBV-miR-BART-22 directly targets the 3'-UTR of MOSPD2 mRNA to promote the EMT and metastasis of NPC cells by activating the Wnt/β-catenin signaling pathway. Our findings provide a potential prognostic biomarker and new insight into the molecular mechanisms of NPC metastasis.
| S-EPMC9338958 | biostudies-literature
Project description:BackgroundAberrant methylation of DNA plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC). In the current study, we aimed to integrate three cohorts profile datasets to identify abnormally methylated-differentially expressed genes and pathways associated with NPC.MethodsData of gene expression microarrays (GSE53819, GSE412452) and gene methylation microarrays (GSE52068) obtained from the GEO database. Aberrantly methylated differentially expressed genes (DEGs) were obtained by GEO2R. The David database was utilized to perform enrichment and functional analysis regarding selected genes. To create a protein-protein interaction (PPI), STRING and Cytoscape software were utilized. The MCODE was used for module analysis of the PPI network.ResultsIn total, 181 hypomethylation-high expression genes were identified, which were enriched in the biological mechanisms involved in the differentiation of endodermal cell, mitotic nuclear division, mitotic cell cycle process, chromosome segregation and cell cycle phase transition, etc. Pathway enrichment showed ECM-receptor interaction, PI3K-Akt signaling pathway, Focal adhesion, Protein digestion and absorption and Amoebiasis, etc. The top 3 hub genes of PPI network were FANCI, POSTN, and IFIH1. Additionally, 210 hypermethylation-low expression genes were identified, and our data revealed enrichment in biological processes including axoneme assembly, micro tubular formation, assembly of axonemal dynein complex, cilium movement and cilium organization, etc. Pathway analysis indicated enrichment in B cell receptor signaling pathway, Hematopoietic cell lineage, Leukocyte transendothelial migration, Complement and coagulation cascades and Fc gamma R-mediated phagocytosis, etc. The ZMYND10, PACRG and POU2AF1 were identified as the top three hub genes of PPI network. After validation in TCGA and GEPIA database, most hub genes remained significant. Patients with high expression of POSTN found to have shorter overall survival, while in patients with high expression of ZMYND10 and POU2AF1 longer overall survival was identified.ConclusionsThe data revealed novel aberrantly methylated-differentially expressed genes and pathways in NPC by bioinformatics analysis, potentially providing novel insights for the molecular mechanisms governing NPC progression. Hub genes including FANCI, POSTN, IFIH1, ZMYND10, PACRG and POU2AF1 might serve as novel biomarkers for precision diagnosis and providing medical treatment for patient with NPC.
| S-EPMC7144954 | biostudies-literature
Project description:In a large-scale radiological catastrophe, it is expected that hundreds and thousands of people could be exposed to radiation. A rapid method is required for triage of casualties to determine proper medical treatment. In this article, mice were exposed to different radiation doses and sera of mice were investigated by surface-enhanced Raman spectroscopy (SERS) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) after total body irradiation (TBI). The results of the present study indicated that differences have widened over time. The different radiation groups showed a slight overlap at 24 h and 72 h but were completely distinct at the 10th day after TBI. The SERS spectrum between the normal group and the irradiated group showed a significant difference at 24 hours. The same trend was depicted in scatting score plots. Significant differences in Raman peaks were found, such as 744 and 1495 cm-1 corresponding to riboflavin and 593 and 1204 cm-1 corresponding to l-tryptophan. The lack of riboflavin and l-tryptophan will influence metabolism levels. Above all, these results bear potential in the development of label-free and rapid tools for on-site detection and screening of irradiation injuries.
| S-EPMC9078126 | biostudies-literature
Project description:Telomerase has been considered as a biomarker for early diagnosis and prognosis assessment of hepatocellular carcinoma (HCC), while the highly sensitive and specific methods remain challenging. To detect telomerase, a novel surface-enhanced Raman scattering (SERS) biosensor was constructed using the dual DNA-catalyzed amplification strategy composed of strand displacement amplification (SDA) and catalytic hairpin assembly (CHA). This strategy relies on the extension reaction of telomerase primer induced by telomerase, forming long-stranded DNAs with repetitive sequence to catalyze the follow-up SDA event. Subsequently, the SDA products can trigger the CHA reaction between the SERS probes (Au-Ag nanocages (Au-AgNCs) modified with hairpin DNA1 and Raman reporters) and capture substrate (Au@SiO2 array labeled with hairpin DNA2), resulting in the formation of numerous "hot spots" to significantly enhance the SERS signal. Results are promising that the established biosensor presented excellent reproducibility, specificity and sensitivity. Moreover, ELISA was applied as the golden standard to verify the application of the proposed biosensor in real samples and the results confirmed the satisfactory accuracy of our method. Therefore, the proposed SERS biosensor has the potential to be an ideal tool for the early screening of HCC.
| S-EPMC9881591 | biostudies-literature
Project description:BACKGROUND:Recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis have opened a new field of utilizing circulating miRNAs as cancer biomarkers. In this pilot study, we conducted for the first time, to our knowledge, the evaluation of the applicability of salivary miRNAs as novel biomarkers for nasopharyngeal carcinoma (NPC) detection. METHODS:Microarray miRNA expression profiling was performed on saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls, and 12 significantly down-regulated miRNAs were selected for quantitative real-time-PCR (qRT-PCR) validation and further analysis. Their target genes enriched by gene ontology and pathway analysis were used to construct regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy. RESULTS:Twelve dysregulated miRNAs screened by microarray that showed the same expression patterns with qRT-PCR analysis. Through bioinformatics analysis, the most prominent hub gene probably regulated by the 12 down-regulated miRNAs is found to be TP53. The ROC including the 12 miRNAs separated NPC patients from healthy controls with very high accuracy (areas under the receiver operating characteristic curve [AUC]?=?0.999, sensitivity?=?100.00%, specificity?=?96.00%). Furthermore, if only six significantly dysregulated miRNAs were selected for the ROC analysis, the accuracy is still impressive (AUC?=?0.941, sensitivity?=?95.45%, specificity?=?80.00%). CONCLUSIONS:This study highlights the potential for salivary miRNAs as biomarkers for the detection of NPC. Meanwhile, differentially expressed miRNAs in saliva might play critical roles in NPC by regulating their target genes, which associated with some significant pathways, such as p53 signaling pathway.
| S-EPMC6712819 | biostudies-literature
Project description:Pathogen-induced inflammation has been one of the intensive research areas in carcinogenesis. EBV encoded RNAs (EBERs) have been suggested to play roles in anti-apoptosis and growth-promotion in lymphoid and immune disorders. However, pathological roles of EBERs in solid tumors of epithelia origin remain to be elucidated. Given their characteristic dsRNA structures, recent studies provided evidences for the activation of some pattern recognition receptors (PRR) by EBERs, which is fundamental in the process of pathogenesis. Here, we show that EBERs induce inflammatory response in nasopharyngeal carcinoma (NPC) cells through Toll-like receptor 3 (TLR3), mainly featured by high level of TNFα production. Interestingly, EBERs and EBV latent membrane protein 1 (LMP1) form a positive regulatory loop with NF-κB as a key node that amplifies the inflammatory signals in EBV infected epithelial cells. We demonstrate in vivo that EBERs can interact with TLR3 and induce tumor cells to produce cytokines in B16 synergetic tumor and human NPC xenograft models, in which macrophages are recruited and activated, leading to a favorable microenvironment for solid tumor growth. Lastly, we verify a positive association between EBER and TNFα levels in NPC clinical samples and the combination of EBER and TNFα expressions provides a predictor of poor survival of NPC patients. In conclusion, EBERs play a pivotal role in inflammation-to-oncogenesis transition in NPC development.
| S-EPMC4695186 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignancy that is prevalent in southern China and Southeast Asia. It is consistently associated with latent Epstein-Barr virus (EBV) infection. In NPC, miR-BARTs, the EBV-encoded miRNAs derived from BamH1-A rightward transcripts, are abundantly expressed and contribute to cancer development by targeting various cellular and viral genes. In this study, we establish a comprehensive transcriptional profile of EBV-encoded miRNAs in a panel of NPC patient-derived xenografts and an EBV-positive NPC cell line by small RNA sequencing. Among the 40 miR-BARTs, predominant expression of 22 miRNAs was consistently detected in these tumors. Among the abundantly expressed EBV-miRNAs, BART5-5p, BART7-3p, BART9-3p, and BART14-3p could negatively regulate the expression of a key DNA double-strand break (DSB) repair gene, ataxia telangiectasia mutated (ATM), by binding to multiple sites on its 3'-UTR. Notably, the expression of these four miR-BARTs represented more than 10% of all EBV-encoded miRNAs in tumor cells, while downregulation of ATM expression was commonly detected in all of our tested sequenced samples. In addition, downregulation of ATM was also observed in primary NPC tissues in both qRT-PCR (16 NP and 45 NPC cases) and immunohistochemical staining (35 NP and 46 NPC cases) analysis. Modulation of ATM expression by BART5-5p, BART7-3p, BART9-3p, and BART14-3p was demonstrated in the transient transfection assays. These findings suggest that EBV uses miRNA machinery as a key mechanism to control the ATM signaling pathway in NPC cells. By suppressing these endogenous miR-BARTs in EBV-positive NPC cells, we further demonstrated the novel function of miR-BARTs in inhibiting Zta-induced lytic reactivation. These findings imply that the four viral miRNAs work co-operatively to modulate ATM activity in response to DNA damage and to maintain viral latency, contributing to the tumorigenesis of NPC. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
| S-EPMC5888186 | biostudies-literature
Project description:To identify metastasis-related proteins in nasopharyngeal carcinoma (NPC), iTRAQ-tagging combined with 2D LC-MS/MS analysis was performed to identify the differentially expressed proteins (DEPs) in high metastatic NPC 5-8F cells and non-metastatic NPC 6-10B cells, and qRT-PCR and Western blotting were used to confirm DEPs. As a result, 101 DEPs were identified by proteomics, and 12 DEPs were selectively validated. We further detected expression of three DEPs (RAN, SQSTM1 and TRIM29) in a cohort of NPC tissue specimens to assess their value as NPC metastatic biomarkers, and found that combination of RAN, SQSTM1 and TRIM29 could discriminate metastatic NPC from non-metastatic NPC with a sensitivity of 88% and a specificity of 91%. TRIM29 and RAN expression level were closely correlated with lymph node and distant metastasis and clinical stage (P <0.05) in NPC patients. Finally, a combination of loss-of-function and gain-of-function approaches was performed to determine the effects of TRIM29 on NPC cell proliferation, migration, invasion and metastasis. The results showed that TRIM29 knockdown significantly attenuated while TRIM29 overexpression promoted NPC cell in vitro proliferation, migration and invasion and in vivo metastasis. The present data first time show that SQSTM1, RAN and TRIM29 are novel potential biomarkers for predicting NPC metastasis, demonstrate that TRIM29 is a metastasis-promoted protein of NPC.
| S-EPMC5085135 | biostudies-literature
Project description:The identification and differentiation of a large number of distinct molecular species with high temporal and spatial resolution is a major challenge in biomedical science. Fluorescence microscopy is a powerful tool, but its multiplexing ability is limited by the number of spectrally distinguishable fluorophores. Here, we used (deoxy)ribonucleic acid (DNA)-origami technology to construct submicrometre nanorods that act as fluorescent barcodes. We demonstrate that spatial control over the positioning of fluorophores on the surface of a stiff DNA nanorod can produce 216 distinct barcodes that can be decoded unambiguously using epifluorescence or total internal reflection fluorescence microscopy. Barcodes with higher spatial information density were demonstrated via the construction of super-resolution barcodes with features spaced by ?40 nm. One species of the barcodes was used to tag yeast surface receptors, which suggests their potential applications as in situ imaging probes for diverse biomolecular and cellular entities in their native environments.
| S-EPMC3523708 | biostudies-literature