GHSR DNA hypermethylation is a common epigenetic alteration of high diagnostic value in a broad spectrum of cancers.
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ABSTRACT:
SUBMITTER: Moskalev EA
PROVIDER: S-EPMC4414200 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Many studies manifested miRNA-628 (miR-628) was deregulated in various cancers, indicating that miR-628 might serve as a novel biomarker of cancer diagnosis and prognosis, but it's role was still uncertain. This study aimed to evaluate the value of miR-628 in various cancers for diagnosis and prognosis, as well as its predictive power in combination biomarkers. Materials and Methods: A literature search was performed using Medline (via PubMed), Embase, Web of Science databases, and Ovid platform up to November 2017. Meta-analysis was performed to provide summative outcomes. Quality assessment of each included study was performed. Results: Twelve articles with 20 studies were included in our meta-analysis, including 8 articles with 15 studies for diagnostic meta-analysis and 4 articles with 5 studies for prognostic meta-analysis. For the diagnostic meta-analysis of miR-628 alone, the overall pooled results for sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic (SROC) curve (AUC) were 0.81 (95% CI: 0.62-0.91), 0.72 (95% CI: 0.48-0.88), 2.90 (95% CI: 1.50-5.40), 0.27 (95% CI: 0.14-0.50), 11.0 (95% CI: 4.00-25.00), and 0.84 (95% CI: 0.80-0.87), respectively. For the diagnostic meta-analysis of miR-628-related combination biomarkers, the above six parameters were 0.89 (95% CI: 0.84-0.92), 0.93 (95% CI: 0.82-0.97), 12.30 (95% CI: 4.70-32.50), 0.12 (95% CI: 0.08-0.19), and 100.00 (95% CI: 28.00-354.00), 0.93 (95% CI: 0.90-0.95), respectively. For the prognostic meta-analysis, patients with lower miR-628 had significant shorter overall survival than high expression of miR-628 (HR = 1.553, 95% CI: 1.041-2.318, z = 2.16, P = 0.031). Conclusions: This study confirms that miR-628 may be a promising biomarker for cancer diagnosis and prognosis. Expertly, microRNAs combination biomarkers could be a new alternative for clinical application.
| S-EPMC5950592 | biostudies-literature
Project description:We sought to investigate the anticancer effects of the novel FOXM1 inhibitor, STL001 in a variety of human cancers from solid tumors including ovarian cancer, colorectal cancer, breast cancer, and prostate cancers. Here, the capacity of the novel compounds STL001 as FOXM1 inhibitor was verified in human cancer cell lines from solid tumors. Further, we showed here that FOXM1 inhibitor STL001 treatment resulted in sensitization of cancer cells to apoptotic death by multiple chemotherapeutic agents. STL001 was studied further to verify its direct target engagement with FOXM1. We have also provided Transcriptome-supported evidence that STL001 exhibits selectivity toward suppressing FOXM1-controlled regulatory pathways. This study verify and characterize a novel FOXM1 inhibitor STL001 that effectively antagonize FOXM1 activity and sensitize a variety of human cancer cells to traditionally used chemotherapy agents, and may be suitable for further clinical evaluation in targeting chemotherapy resistance human cancers.
2024-05-08 | GSE261182 | GEO
Project description:BACKGROUND: We have previously reported that expression of the Wnt antagonist genes SFRP1 and SFRP5 is frequently silenced by promoter hypermethylation in breast cancer. SFRP2 is a further Wnt inhibitor whose expression was recently found being downregulated in various malignancies. Here we investigated whether SFRP2 is also implicated in human breast cancer, and if so whether SFRP2 promoter methylation might serve as a potential tumor biomarker. METHODS: We analyzed SFRP2 mRNA expression and SFRP2 promoter methylation in 10 breast cell lines, 199 primary breast carcinomas, 20 matched normal breast tissues and 17 cancer-unrelated normal breast tissues using RT-PCR, realtime PCR, methylation-specific PCR and Pyrosequencing, respectively. SFRP2 protein expression was assessed by immunohistochemistry on a tissue microarray. Proliferation assays after transfection with an SFRP2 expression vector were performed with mammary MCF10A cells. Statistical evaluations were accomplished with SPSS 14.0 software. RESULTS: Of the cancerous breast cell lines, 7/8 (88%) lacked SFRP2 mRNA expression due to SFRP2 promoter methylation (P < 0.001). SFRP2 expression was substantially restored in most breast cell lines after treatment with 5-aza-2'-deoxycytidine and trichostatin A. In primary breast carcinomas SFRP2 protein expression was strongly reduced in 93 of 125 specimens (74%). SFRP2 promoter methylation was detected in 165/199 primary carcinomas (83%) whereas all cancer-related and unrelated normal breast tissues were not affected by SFRP2 methylation. SFRP2 methylation was not associated with clinicopathological factors or clinical patient outcome. However, loss of SFRP2 protein expression showed a weak association with unfavorable patient overall survival (P = 0.071). Forced expression of SFRP2 in mammary MCF10A cells substantially inhibited proliferation rates (P = 0.045). CONCLUSION: The SFRP2 gene is a high-frequent target of epigenetic inactivation in human breast cancer. Its methylation leads to abrogation of SFRP2 expression, conferring a growth advantage to epithelial mammary cells. This altogether supports a tumor suppressive function of SFRP2. Although clinical patient outcome was not associated with SFRP2 methylation, the high frequency of this epimutation and its putative specificity to neoplastic cells may qualify SFRP2 promoter methylation as a potential candidate screening marker helping to improve early breast cancer detection.
| S-EPMC2613402 | biostudies-literature
Project description:The Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a mitotic checkpoint and tumor-suppressor gene, its loss contributes tumorigenesis of epithelial cancers including colorectal carcinoma (CRC). The diagnostic and prognostic value of CHFR promoter hypermethylation in CRC remains unclear. This study aimed to conduct a meta-analysis and literature review and investigate clinicopathological significance of CHFR promoter hypermethylation in CRC. The following online database were used: PubMed, EMBASE, and Web of Science up to March 2017. Odds Ratios (OR) and Hazard Ratios (HR) with 95% corresponding confidence intervals (CIs) were calculated. A total of seven relevant articles were available for meta-analysis which included 966 patients. The frequency of CHFR promoter hypermethylation significantly increased in CRC compared to normal colorectal mucosa tissue, pooled OR was 8.35, p < 0.00001. CHFR promoter hypermethylation was not significantly correlated to stage, OR was 1.16, p = 0.63. However, CHFR promoter hypermethylation was more frequently observed in CRC with positive lymph nodes metastasis than CRC with negative lymph nodes metastasis, OR was 0.46, p = 0.03. Additionally CHFR promoter hypermethylation was significantly related to poor overall survival in patients with CRC, HR was 0.62, p = 0.008. Based on these results, tumor CHFR promoter hypermethylation is not only a diagnostic biomarker for CRC, but also a prognostic marker. CHFR promoter hypermethylation is significantly associated with worse overall survival in patients with CRC. Our data suggested that CHFR could be a potential drug target for development of demethylation treatment for patients with CRC.
| S-EPMC5687676 | biostudies-literature
Project description:Key messageA major QTL on chromosome 6DL corresponding to bunt resistance gene Bt11 was identified in four mapping populations generated through crosses with Bt11-carriers PI 166910 and M822123. Common bunt in wheat has witnessed a renaissance with the rise of organic agriculture that began in the 1980s. The abandonment of systemic fungicides in organic farming, together with a lack of resistant cultivars, has led to wide-spread problems due to common bunt infections. Knowledge about genetic sources for resistance is still scarce and only few of the known bunt resistance factors are currently used in breeding. We therefore aimed to map the resistance factor harboured by the Turkish landrace PI 166910, which is the resistance donor for the Bt11 bunt differential line. Four mapping populations (MPs) with 96-132 recombinant inbred lines (RILs) were phenotyped for common bunt resistance over 2, 3 or 4 years with one or two local bunt populations and genotyped with the 25K SNP array. A major bunt resistance locus on the distal end of chromosome 6D designated QBt.ifa-6DL was identified in all MPs and experiments. Additional QTL contributing to resistance were detected on chromosomes 4B, 1A, 1B, 2A and 7B. QBt.ifa-6DL mapped to a region overlapping with the Bt9-locus identified in previous studies, but results indicate that QBt.ifa-6DL is different from Bt9 and convincing evidence from haplotype comparisons suggests that it represents the Bt11 resistance allele. Markers for the distal region of chromosome 6D between 492.6 and 495.2 Mbp can be used to select for QBt.ifa-6DL. This resistance factor confers high and stable resistance against common bunt and should be integrated into organic and low-input wheat breeding programs.
| S-EPMC10485103 | biostudies-literature
Project description:BackgroundPopulations in north central China are at high risk for oesophageal squamous cell carcinoma (ESCC) and gastric cancer (GC), and genetic variation in epigenetic machinery genes and pathways may contribute to this risk.MethodsWe used the adaptive multilocus joint test to analyse 192 epigenetic genes involved in chromatin remodelling, DNA methylation and microRNA biosynthesis in 1942 ESCC and 1758 GC cases [1126 cardia (GCA) and 632 non-cardia adenocarcinoma (GNCA)] and 2111 controls with Chinese ancestry. We examined potential function of risk alleles using in silico and expression quantitative trait loci (eQTLs) analyses.ResultsSuggestive pathway-based associations were observed for the overall epigenetic (P-value(PATH) = 0.034) and chromatin remodelling (P-value(PATH) = 0.039) pathways with risk of GCA, but not GC, GNCA or ESCC. Overall, 37 different epigenetic machinery genes were associated with risk of one or more upper gastrointestinal (UGI) cancer sites (P-value(GENE )< 0.05), including 14 chromatin remodelling genes whose products are involved in the regulation of HOX genes. We identified a gastric eQTL (rs12724079; rho = 0.37; P = 0.0006) which regulates mRNA expression of ASH1L. Several suggestive eQTLs were also found in oesophageal (rs10898459 in EED), gastric cardia (rs7157322 in DICER1; rs8179271 in ASH1L), and gastric non-cardia (rs1790733 in PPP1CA) tissues.ConclusionsResults of our analyses provide limited but suggestive evidence for a role of epigenetic gene variation in the aetiology of UGI cancer.
| S-EPMC4598798 | biostudies-literature
Project description:BackgroundBlood cultures, and molecular diagnostic tests that directly detect pathogen DNA in blood, fail to detect bloodstream infections in most infected patients. Thus, there is a need for a rapid test that can diagnose the presence of infection to triage patients, guide therapy, and decrease the incidence of sepsis.MethodsAn Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) that uses magnetic microbeads coated with an engineered version of the human opsonin, Mannose Binding Lectin, containing the Fc immunoglobulin domain linked to its carbohydrate recognition domain (FcMBL) was developed to quantify pathogen-associated molecular patterns (PAMPs) in whole blood. This assay was tested in rats and pigs to explore whether it can detect infections and monitor disease progression, and in prospectively enrolled, emergency room patients with suspected sepsis. These results were also compared with data obtained from non-infected patients with or without traumatic injuries.ResultsThe FcMBL ELLecSA was able to detect PAMPS present on, or released by, 85% of clinical isolates representing 47 of 55 different pathogen species, including the most common causes of sepsis. The PAMP assay rapidly (<1h) detected the presence of active infection in animals, even when blood cultures were negative and bacteriocidal antibiotics were administered. In patients with suspected sepsis, the FcMBL ELLecSA detected infection in 55 of 67 patients with high sensitivity (>81%), specificity (>89%), and diagnostic accuracy of 0·87. It also distinguished infection from trauma-related inflammation in the same patient cohorts with a higher specificity than the clinical sepsis biomarker, C-reactive Protein.ConclusionThe FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated. It may help to triage patients with suspected systemic infections, and serve as a companion diagnostic to guide administration of emerging dialysis-like sepsis therapies.
| S-EPMC4972566 | biostudies-literature
Project description:BackgroundFungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leading causes of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance are two major deleterious issues associated with existing antifungal agents. Increasing a host's tolerance and/or immunity to fungal pathogens has potential to alleviate these problems. A host's tolerance may be improved by modulating the immune system such that it responds more rapidly and robustly in all facets, ranging from the recognition of pathogens to their clearance from the host. An understanding of biological processes and genes that are perturbed during attempted fungal exposure, colonization, and/or invasion will help guide the identification of endogenous immunomodulators and/or small molecules that activate host-immune responses such as specialized adjuvants.ResultsIn this study, we present computational techniques and approaches using publicly available transcriptional data sets, to predict immunomodulators that may act against multiple fungal pathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically significant associations between host responses to A. fumigatus and C. albicans. Our analysis identified biological processes that were consistently perturbed by these two pathogens. These processes contained both immune response-inducing genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of common immunomodulators that can potentially be activated or suppressed (agonized or antagonized) in order to render the host more tolerant to infections caused by A. fumigatus and C. albicans.ConclusionsOur computational approaches and methodologies described here can now be applied to newly generated or expanded data sets for further elucidation of additional drug targets. Moreover, identified immunomodulators may be used to generate experimentally testable hypotheses that could help in the discovery of broad-spectrum immunotherapeutic interventions. All of our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc.
| S-EPMC3853472 | biostudies-literature
Project description:Human telomerase reverse transcriptase (hTERT) plays a critical role in the pathogenesis of human malignancies. Overexpression of hTERT is essential in controlling the propagation of cancer cells. The CpG island located at hTERT promoter region is subjected to methylation modification in human cancer. In this perspective article, we discussed the diagnostic value of methylated hTERT in human cancers. The definitive diagnosis of most solid tumors is based on histological and immunohistochemical features. Under certain circumstances, however, the use of methylated hTERT might be useful in overcoming the limitation of the conventional methods. Methylated hTERT showed a good diagnostic power in discriminating cancer from benign or normal tissues. Nevertheless, differences in detection method, methylation site, cancer type, and histological subtype of cancer make it difficult to evaluate the actual diagnostic accuracy of methylated hTERT. Therefore, we performed subgroup analysis to assess the effects of these factors on the diagnostic efficiency of methylated hTERT. We demonstrated that quantitative MSP (qMSP) assay offers the highest discriminative power between normal and cancer in comparison with different detection methods. In addition, the methylated sites selected by different studies had an impact on the detection performance. Moreover, the diagnostic power of methylated hTERT was affected by cancer type and histological subtype. In conclusion, the existing evidence demonstrated that methylated hTERT is effective in cancer detection. Detailed profiling of the methylation sites to local the common methylation hotspot across human cancers is warranted to maximize the diagnostic value of methylated hTERT in cancer detection.
| S-EPMC4689846 | biostudies-literature
Project description:Tissue microRNAs (miRNAs) can detect cancers and predict prognosis. Several recent studies reported that tissue, plasma, and saliva miRNAs share similar expression profiles. In this study, we investigated the diagnostic value of salivary miRNAs (including whole saliva and saliva supernatant) for detection of esophageal cancer. By Agilent microarray, six deregulated miRNAs from whole saliva samples from seven patients with esophageal cancer and three healthy controls were selected. The six selected miRNAs were subjected to validation of their expression levels by RT-qPCR using both whole saliva and saliva supernatant samples from an independent set of 39 patients with esophageal cancer and 19 healthy controls.
2012-10-03 | E-GEOD-41268 | biostudies-arrayexpress