Alu methylation serves as a biomarker for non-invasive diagnosis of glioma.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen J
PROVIDER: S-EPMC5041967 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:MicroRNAs (miRs) transferred by exosomes can function as non-invasive potential biomarkers for the diagnosis and prognosis in various types of cancer. The present study examined the diagnostic and prognostic value of serum exosomal-(exo-)miR-210 levels in association with hypoxic conditions in patients with glioma. Serum levels of exo-miR-210 were determined by quantitative PCR in samples obtained from patients with glioma. Patients were divided into low-and high-expression exo-miR-210 groups according to the median expression value. Statistical analyses were conducted to examine the potential value of exo-miR-210 in predicting the diagnosis and prognosis of patients with glioma. A significant increase in serum exo-miR-210 levels was observed in patients with glioma compared with healthy controls. Additionally, the expression levels of exo-miR-210 were increased with ascending pathological grades. Furthermore, expression levels of miR-210 in serum exosomes from patients with glioblastoma were markedly decreased following surgery and upregulated once more at the recurrences of primary tumors, indicating that exo-miR-210 could reflect alterations in malignant glioma loads. In addition, Kaplan-Meier analysis was performed to analyze overall survival (OS) time. Patients with malignant glioma with high exo-miR-210 expression exhibited a poorer OS compared with patients with low expression. Importantly, univariate and multivariate Cox regression analysis revealed that the expression levels of exo-miR-210 in glioma serum samples were independently associated with OS. Finally, increased serum exo-miR-210 expression was positively associated with high levels of hypoxia-inducible factor 1a and reflected hypoxia in patients with glioma. In conclusion, serum levels of exo-miR-210 may serve as a diagnostic, prognostic and hypoxic biomarker to reflect glioma status and hypoxic signatures.
| S-EPMC7039075 | biostudies-literature
Project description:Increasing evidence has verified that small nucleolar RNAs (snoRNAs) play significant roles in tumorigenesis and exhibit prognostic value in clinical practice. In the study, we analysed the expression profile and clinical relevance of snoRNAs from TCGA database including 530 ccRCC (clear cell renal cell carcinoma) and 72 control cases. By using univariate and multivariate Cox analysis, we established a six-snoRNA signature and divided patients into high-risk or low-risk groups. We found patients in high-risk group had significantly shorter overall survival and recurrence-free survival than those in low-risk group in test series, validation series and entire series by Kaplan-Meier analysis. We also confirmed this signature had a great accuracy and specificity in 64 clinical tissue cases and 50 serum samples. Then, depending on receiver operating characteristic curve analysis we found the six-snoRNA signature was an superior indicator better than conventional clinical factors (AUC = 0.732). Furthermore, combining the signature with TNM stage or Fuhrman grade were the optimal indicators (AUC = 0.792; AUC = 0.800) and processed the clinical applied value for ccRCC. Finally, we found the SNORA70B and its hose gene USP34 might directly regulate Wnt signalling pathway to promote tumorigenesis in ccRCC. In general, our study established a six-snoRNA signature as an independent and superior diagnosis and prognosis indicator for ccRCC.
| S-EPMC7011154 | biostudies-literature
Project description:Gallbladder carcinoma (GBC) is the most common biliary tract malignant tumor. However, few diagnostic and prognostic biomarkers are available. Although the potential role of exosomes in the diagnosis of several tumor types has been repeatedly explored, the use of exosomal microRNAs (miRNAs) as specific biomarkers for GBC has not been systematically conducted. In this study, we identified a 5-exosomal miRNAs set that can be used to evaluate the risk of GBC through a three-step study that relies on biomarker discovery, training and validation. This biomarker set including the exosomal miR-552-3p, miR-581, miR-4433a-3p, miR-496, and miR-203b-3p.
2022-09-15 | GSE176159 | GEO
Project description:BackgroundThe intestinal flora is correlated with the occurrence of colorectal cancer. We evaluate a new predictive model for the non-invasive diagnosis of colorectal cancer based on intestinal flora to verify the clinical application prospects of the intestinal flora as a new biomarker in non-invasive screening of colorectal cancer.MethodsSubjects from two independent Asian cohorts (cohort I, consisting of 206 colorectal cancer and 112 healthy subjects; cohort II, consisting of 67 colorectal cancer and 54 healthy subjects) were included. A probe-based duplex quantitative PCR (qPCR) determination was established for the quantitative determination of candidate bacterial markers.ResultsWe screened through the gutMEGA database to identify potential non-invasive biomarkers for colorectal cancer, including Prevotella copri (Pc), Gemella morbillorum (Gm), Parvimonas micra (Pm), Cetobacterium somerae (Cs), and Pasteurella stomatis (Ps). A predictive model with good sensitivity and specificity was established as a new diagnostic tool for colorectal cancer. Under the best cutoff value that maximizes the sum of sensitivity and specificity, Gm and Pm had better specificity and sensitivity than other target bacteria. The combined detection model of five kinds of bacteria showed better diagnostic ability than Gm or Pm alone (AUC = 0.861, P < 0.001). These findings were further confirmed in the independent cohort II. Particularly, the combination of bacterial markers and fecal immunochemical test (FIT) improved the diagnostic ability of the five bacteria (sensitivity 67.96%, specificity 89.29%) for patients with colorectal cancer.ConclusionFecal-based colorectal cancer-related bacteria can be used as new non-invasive diagnostic biomarkers of colorectal cancer. Simultaneously, the molecular biomarkers in fecal samples are similar to FIT, have the applicability in combination with other detection methods, which is expected to improve the sensitivity of diagnosis for colorectal cancer, and have a promising prospect of clinical application.
| S-EPMC8719628 | biostudies-literature
Project description:BackgroundThoracic aortic dissection (TAD) is a severe disease with limited understandings in its pathogenesis. Altered DNA methylation has been revealed to be involved in many diseases etiology. Few studies have examined the role of DNA methylation in the development of TAD. This study explored alterations of the DNA methylation landscape in TAD and examined the potential role of cell-free DNA (cfDNA) methylation as a biomarker in TAD diagnosis.ResultsAscending aortic tissues from TAD patients (Stanford type A; n = 6) and healthy controls (n = 6) were first examined via whole-genome bisulfite sequencing (WGBS). While no obvious global methylation shift was observed, numerous differentially methylated regions (DMRs) were identified, with associated genes enriched in the areas of vasculature and heart development. We further confirmed the methylation and expression changes in homeobox (Hox) clusters with 10 independent samples using bisulfite pyrosequencing and quantitative real-time PCR (qPCR). Among these, HOXA5, HOXB6 and HOXC6 were significantly down-regulated in TAD samples relative to controls. To evaluate cfDNA methylation pattern as a biomarker in TAD diagnosis, cfDNA from TAD patients (Stanford type A; n = 7) and healthy controls (n = 4) were examined by WGBS. A prediction model was built using DMRs identified previously from aortic tissues on methylation data from cfDNA. Both high sensitivity (86%) and specificity (75%) were achieved in patient classification (AUC = 0.96).ConclusionsThese findings showed an altered epigenetic regulation in TAD patients. This altered epigenetic regulation and subsequent altered expression of genes associated with vasculature and heart development, such as Hox family genes, may contribute to the loss of aortic integrity and TAD pathogenesis. Additionally, the cfDNA methylation in TAD was highly disease specific, which can be used as a non-invasive biomarker for disease prediction.
| S-EPMC8186232 | biostudies-literature
Project description:Lower-grade glioma (LGG) is a diffuse infiltrative tumor of the central nervous system, which lacks targeted therapy. We investigated the role of Podocan-like 1 (PODNL1) methylation in LGG clinical outcomes using the TCGA-LGG transcriptomics dataset. We identified four PODNL1 CpG sites, cg07425555, cg26969888, cg18547299, and cg24354933, which were associated with unfavorable overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analysis after adjusting for age, gender, tumor-grade, and IDH1-mutation. In multivariate analysis, the OS and DFS hazard ratios ranged from 0.44 to 0.58 (p < 0.001) and 0.62 to 0.72 (p < 0.001), respectively, for the four PODNL1 CpGs. Enrichment analysis of differential gene and protein expression and analysis of 24 infiltrating immune cell types showed significantly increased infiltration in LGGs and its histological subtypes with low-methylation levels of the PODNL1 CpGs. High PODNL1 expression and low-methylation subgroups of the PODNL1 CpG sites were associated with significantly increased PD-L1, PD-1, and CTLA4 expressions. PODNL1 methylation may thus be a potential indicator of immune checkpoint blockade response, and serve as a biomarker for determining prognosis and immune subtypes in LGG.
| S-EPMC8625785 | biostudies-literature
Project description:Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening.
| S-EPMC6636289 | biostudies-literature
Project description:DDX60, an interferon (IFN)-inducible gene, plays a promotional role in many tumors. However, its function in glioma remains unknown. In this study, bioinformatic analysis (TCGA, CGGA, Rembrandt) illustrated the upregulation and prognostic value of DDX60 in gliomas. Immunohistochemical staining of clinical samples (n = 49) validated the DDX60 expression is higher in gliomas than in normal tissue (n = 20, P < 0.0001). It also could be included in nomogram as a parameter to predict the 3- and 5-year survival risk (C-index = 0.86). The biological process of DDX60 in glioma was mainly enriched in the inflammatory and immune response by GSEA and GO analysis. DDX60 expression had a positive association with most inflammatory-related functions, such as hematopoietic cell kinase (HCK) (R = 0.31), interferon (R = 0.72), STAT1 (R = 54), and a negative correlation with IgG (R = -0.24). Furthermore, DDX60 expression tends to be positively related to multiple infiltrating immune cells, while negatively related to CD56 dim nature killer cell in glioma. Some important immune checkpoints, like CTLA-4, PD-L1, EGF, CD96, and CD226, were all positively related with DDX60 (all Pearson correlation R > 0.26). The expression and correlation between DDX60, EGF, and PD-L1 were confirmed by western blot in clinical samples (n = 14, P < 0.0001) and GBM cells. These results indicated that DDX60 might have important clinical significance in glioma and could serve as a potential immune therapeutic target.
| S-EPMC8222729 | biostudies-literature
Project description:Alzheimer's disease (AD) is the most prevalent form of dementia. Biomarkers such as levels of amyloid beta (Aβ) in cerebrospinal fluid and ApoE genotyping were suggested for the diagnosis of AD, however, the result is either non-conclusive or with invasive procedure. Genome-wide association studies (GWASs) for AD suggested single nucleotide polymorphisms (SNPs) in many genes are associated with the risk of AD, but each only contributed with small effect to the disease. By incorporating a panel of established genetic susceptibility factors, the risk of an individual in getting AD could be better estimated. Further research will be required to reveal if adding to the current well-developed clinical diagnosis protocol, the accuracy and specificity of diagnosis of AD would be greatly improved and if this might also be beneficial in identifying pre-symptomatic AD patients for early diagnosis and intervention of the disease.
| S-EPMC3569084 | biostudies-literature
Project description:Background:Hepatocellular carcinoma (HCC) is an aggressive malignancy with high incidence rate and poor prognosis. Enolase-1 (ENO1), a key glycolytic enzyme, has been implicated in the tumorigenesis of various cancers. However, its diagnostic value and clinical significance in HCC are unclear. Methods:Data of 374 HCC tissues and 50 nontumor tissues were retrieved from The Cancer Genome Atlas database, and the expression level of ENO1 mRNA in HCC was evaluated. In addition, a meta-analysis of 12 HCC cohorts deposited in the Gene Expression Omnibus database was conducted to determine ENO1 expression levels. The diagnostic power of ENO1 in distinguishing HCC tissues from non-HCC tissues was confirmed by receiver operating characteristic (ROC) curve analysis. A tissue microarray comprising 93 HCC specimens and 87 adjacent normal specimens was used to validate ENO1 expression, and its prognostic value in HCC was ascertained by Kaplan-Meier analysis and Cox regression models. In addition, the gene set enrichment analysis was performed to predict the molecular mechanism of ENO1 action in HCC. Results:ENO1 was overexpressed in HCC tissues and associated with worse outcomes in terms of overall survival (OS) (P<0.01) and disease-free survival (P<0.01). ENO1 expression (P<0.01) was an independent prognostic variable for the OS of HCC patients. Moreover, as per the ROC curve analysis, it had good diagnostic power as well. In addition, elevated expression of ENO1 was significantly correlated with the cell cycle and DNA replication pathway, consistent with its association with pro-proliferative genes such as MKI67, PCNA, CDK4, CDK2, and MELK. Conclusion:ENO1 was markedly upregulated and was an oncogene-associated protein in HCC. It is a promising prognostic and diagnostic biomarker for HCC.
| S-EPMC6245378 | biostudies-literature