A practical method to screen and identify functioning biomarkers in nasopharyngeal carcinoma.
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ABSTRACT:
SUBMITTER: Liu C
PROVIDER: S-EPMC8012388 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BACKGROUND:Aberrant 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. METHODS:Data 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. RESULTS:In 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. CONCLUSIONS:The 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:The functional movement screen (FMS) is commonly used to evaluate sports injury risks, but no study has been reported for Wushu athletes. The aim of this study was to identify optimal FMS cut-off points for previously injured Wushu athletes and to examine the associations with other possible factors. In this study, a total of 84 Chinese Wushu athletes (15.1 ± 4.5 years old, 51% male) with a minimum of two years of professional training background in either Taiji, Changquan, or Nanquan were assessed by the FMS. Video recordings were used to confirm the scoring criteria, and previous injuries were assessed based on face-to-face interviews. An optimal cut-off of the FMS score was investigated by receiver operating characteristic curves with sensitivity and specificity. We found that FMS score of less than 16 (sensitivity = 80%, specificity = 56%) was related to an increased occurrence of injuries (odds ratio = 5.096, 95%CI: 1.679-15.465) for the current study sample. The training type and training levels were related with FMS scores. More than half of the athletes (58%) had FMS asymmetry and 21% of athletes reported pain while performing the FMS protocol. Future prospective studies are recommended to use FMS with cut-off of 16 points in Wushu athletes.
| S-EPMC7829906 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC) is the eighth cause of cancer-related deaths worldwide. To screen potential biomarkers associated with early recurrence/metastasis (R/M) of ESCC patients after radical resection, ESCC patients were analyzed by a comparative proteomics analysis using iTRAQ with RPLC-MS to screen differential proteins among R/M groups and adjacent normal tissues. The proteins were identified by qRT-PCR, Western blotting, and tissue microarray. The protein and mRNA expression difference of PHB2 between tumor tissues of ESCC patients and adjacent normal tissues, ESCC patients with and without metastasis, four ESCC cell lines and normal esophageal epithelial cells were inspected using immunohistochemical staining, qRT-PCR, and Western blotting. The EC109 and TE1 cells were used to establish PHB2 knockdown cell models, and their cell proliferation and invasion ability were determined by cell counting method, Transwell® assay. Thirteen proteins were selected by cutoff value of 0.67 fold for underexpression and 1.5-fold for overexpression. Seven proteins were confirmed to be associated with R/M among the 13 proteins. The potential biomarker PHB2 for early recurrence/metastasis of ESCC was identified. PHB2 expression was related to the OS of ESCC patients (P = 0.032) and had high levels in the tumor tissues and human cell lines of ESCC (P = 0.0002). Also, the high PHB2 expression promoted the metastasis of ESCC (P = 0.0075), suggesting high PHB2 expression was a potential prognostic biomarker. Experiments showed that PHB2 could significantly promote the proliferation and cell invasion ability of human ESCC cell lines and the knockdown of PHB2 suppressed the phosphorylation level of AKT, as well as the expression of MMP9 and RAC1. PHB2 could predict the early metastasis of ESCC patients.
| S-EPMC6010861 | biostudies-literature
Project description:Background: Nasopharyngeal carcinoma (NPC) is a malignant nasopharyngeal disease with a complicated etiology that occurs mostly in southern China. Intestinal flora imbalance is believed to be associated with a variety of organ malignancies. Current studies revealed that the destruction of intestinal flora is associated with NPC, and many studies have shown that intestinal flora can be used as a biomarker for many cancers and to predict cancer. Methods: To compare the differences in intestinal flora compositions and biological functions among 8 patients with familial NPC (NPC_F), 24 patients with sporadic NPC (NPC_S), and 27 healthy controls (NOR), we compared the intestinal flora DNA sequencing and hematological testing results between every two groups using bioinformatic methods. Results: Compared to the NOR group, the intestinal flora structures of the patients in the NPC_F and NPC_S groups showed significant changes. In NPC_F, Clostridium ramosum, Citrobacter spp., Veillonella spp., and Prevotella spp. were significantly increased, and Akkermansia muciniphila and Roseburia spp. were significantly reduced. In NPC_S, C. ramosum, Veillonella parvula, Veillonella dispar, and Klebsiella spp. were significantly increased, and Bifidobacterium adolescentis was significantly reduced. A beta diversity analysis showed significant difference compared NPC_F with NOR based on Bray Curtis (P = 0.012) and Unweighted UniFrac (P = 0.0045) index, respectively. The areas under the ROC curves plotted were all 1. Additionally, the concentrations of 5-hydroxytryptamine (5-HT) in NPC_F and NPC_S were significantly higher than those of NOR. C. ramosum was positively correlated with 5-HT (rcm: 0.85, P < 0.001). A functional analysis of the intestinal flora showed that NPC_F was associated with Neurodegenerative Diseases (P = 0.023) and that NPC_S was associated with Neurodegenerative Diseases (P = 0.045) as well. Conclusion: We found that NPC was associated with structural imbalances in the intestinal flora, with C. ramosum that promoted the elevation of 5-HT and opportunistic pathogens being significantly increased, while probiotics significantly decreased. C. ramosum can be used as a novel biomarker and disease prediction models should be established for NPC. The new biomarkers and disease prediction models may be used for disease risk prediction and the screening of high-risk populations, as well as for the early noninvasive diagnosis of NPC.
| S-EPMC6908496 | biostudies-literature
Project description:BACKGROUND:Tissue specimens for nasopharyngeal carcinoma (NPC) research are scarce because of sampling difficulties. Previous studies have suggested non-invasive nasopharyngeal brushing as an effective sampling method for NPC diagnosis. The present study aimed to evaluate the feasibility of nasopharyngeal brushing in the acquisition of NPC nucleic acids for research. METHODS:Nasopharyngeal brushing samples were acquired from 24 healthy individuals and 48 NPC patients. Tissues from 48 NPC and 18 nasopharyngitis patients were collected by endoscopic biopsy. The expression levels of tumor suppressor genes (TSGs) and Epstein-Barr virus (EBV)-encoded microRNAs as well as EBV DNA copy number were measured by quantitative polymerase chain reaction in both types of samples. RESULTS:Among six TSGs examined, the expression levels of two genes were significantly decreased in nasopharyngeal brushing and tissue samples from NPC patients as compared with those from healthy/nasopharyngitis individuals. Four EBV-encoded microRNAs, mir-bart1-5p, mir-bart5, mir-bart6-5p, and mir-bart17-5p, were significantly up-regulated in both NPC brushing and tissue samples compared with those from healthy/nasopharyngitis controls (P?<?0.001). EBV DNA was significantly increased in both nasopharyngeal brushing samples (P?<?0.001) and tissue samples (P?<?0.001) from NPC patients in comparison with those from healthy controls. CONCLUSIONS:Nasopharyngeal brushing can obtain sufficient tumoral materials for the analysis of viral nucleic acid, including EBV-encoded microRNAs and EBV DNA. For the detection of TSG expression, nasopharyngeal brushings was feasible but inferior to tissue samples. This study confirms nasopharyngeal brushing as an applicable sampling method that can aid in nucleic acid-based NPC research.
| S-EPMC5993107 | biostudies-literature
Project description:Background:In recent years, miR-152 has been dysregulated in a variety of tumors and used as a tumor suppressor. Nevertheless, its role in nasopharyngeal carcinoma (NPC) remains unidentified. Materials and methods:Real-time quantitative PCR (polymerase chain reaction) was performed to analyze the expression of miR-152 in NPC cell lines. MiR-152 expression profiles in NPC tissues were obtained from Gene Expression Omnibus (GEO GSE36682). The effect of miR-152 on the invasion and proliferation of NPC cells was determined through cell invasion, wound healing, and cell viability assays. Apoptosis was examined by flow cytometry, and Western blot was performed to measure expression of the target gene. Pyrosequencing was used to detect the methylation level of NPC cells. Results:In this study, miR-152 was downregulated in the NPC tissues and cell lines. When miR-152 was enhanced, the invasion and migration of NPC cells were inhibited. However, miR-152 had no effect on the proliferation of NPC cells. Luciferase reporter gene analysis was performed, and the results showed that DNMT1 (DNA (cytosine-5)-methyltransferase 1) is a direct target of miR-152 in NPC cells. DNMT1 downregulation and miR-152 overexpression both reversed the effects of miR-152 inhibition on the NPC cells. In addition, miR-152 expression increased as a result of the inhibition of the methylation level of miR-152 when DNMT1 expression was downregulated. Conclusion:The overexpression of miR-152 inhibited the migration and invasion of NPC cells by targeting DNMT1. Furthermore, DNMT1 regulated miR-152 expression through DNA methylation. Overall, the novel miR-152-DNMT1 regulatory circuit may provide better understanding of the pathogenesis of NPC and new epigenetic therapeutic target in NPC.
| S-EPMC5877490 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that shows a remarkable ethnic and geographical distribution. It is one of the major public health problems in some countries, especially Southern China and Southeast Asia, but rare in most Western countries. Multifactorial interactions such as Epstein-Barr virus infection, individual's genetic susceptibility, as well as environmental and dietary factors may facilitate the pathogenesis of this malignancy. Late presentation and the complex nature of the disease have led it to become a major cause of mortality. Therefore, an effective, sensitive, and specific molecular biomarker is urgently needed for early disease diagnosis, prognosis, and prediction of metastasis and recurrence after treatment. In this review, we discuss the recent research status of potential biomarker discovery and the problems that need to be explored further for better NPC management. By studying the aberrant pattern of these candidate biomarkers that promote NPC development and progression, we are able to understand the complexity of this malignancy better, hence positing our stands better towards strategies that may provide a way forward to the discovery of more reliable and specific biomarkers for diagnosis and targeted therapeutic development.
| S-EPMC8305767 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC) is the most common malignant tumor with a remarkable racial and geographical distribution including people in southern China, South East Asia, and the Middle East/North Africa. DNA methylation is an important manifestation of epigenetic modification, has been studied over several decades, and by regulating and controlling the expression of cancer-related genesits, abnormal DNA methylation can influence in a variety of human malignancy tumors.Until now, there is no analysis focus on differentially methylated, differential expressed genes (MDEGs) study, so we make a joint analysis for both gene methylation profiling microarray and gene expression profiling microarray in NPC. Two gene expression datasets (GSE64634 and GSE12452) and gene methylation profiling data set (GSE62336) were downloaded from GEO and analyzed using the online tool GEO2R to identify MDEGs. Gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differentially methylated genes were performed. The STRING database was used to evaluate the interactions of MDEGs and to construct a protein-protein interaction (PPI) network using Cytoscape software. Hub genes were validated with the cBioPortal database.The overlap among the 3 datasets contained 135 hypermethylation genes and 541 hypomethylation genes between NPC and non-NPC samples. A total of 4 genes (TROAP, PCOLCE2, HOXA4, and C1QB) in Hyper-LGs and 14 genes (DYNC1H1, LNX1, RAB37, ALDH3A1, SLC24A4, CP, CEP250, ANK2, DNAI2, MUC13, ACACB, GABRP, STX7, and TTC9) in Hypo-HGs were identified as hub genes.The study of DNA methylation and gene expression provides us a strong support as well as new comprehensive information of MDEGs to the revelation of nasopharyngeal carcinoma's complex pathogenesis. However, further studies are needed to elucidate the biological function of these genes in NPC in the future.
| S-EPMC7302588 | biostudies-literature
Project description:The past years have witnessed the vigorous development of immunotherapy, mainly immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Indeed, ICIs have largely revolutionized the management and improved the prognosis of patients with intermediate and advanced hepatocellular carcinoma (HCC). However, biomarker-based stratification of HCC patients for optimal response to ICI treatment is still of unmet need and again, there exists the necessity to dynamically monitor treatment effect in real-time manner. The role of conventional biomarkers in immunotherapy surveillance is largely limited by spatial and temporal tumor heterogeneity whereas liquid biopsy seems to be promising to circumvent tumor heterogeneity to identify candidate patients who may response to immunotherapy, to dynamically monitor treatment effect and to unveil resistance mechanism. Herein, we provide a thorough review about the potential utility of liquid biopsy in immunotherapy for HCC and discuss its future perspectives.
| S-EPMC8686238 | biostudies-literature
Project description:Study on the relieving effect and mechanism of probiotics combination on mucositis induced by radiotherapy and chemotherapy targeting nasopharyngeal carcinoma Raw sequence reads
| PRJNA579226 | ENA