Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Herceg Z
PROVIDER: S-EPMC5543860 | biostudies-other | 2007 Jun
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Colorectal cancer (CRC) is one of the most common cancer worldwide and results from the accumulation of mutations and epimutations in colonic mucosa cells ultimately leading to cell proliferation and metastasis. Unfortunately, CRC prognosis is still poor and the search of novel diagnostic and prognostic biomarkers is highly desired to prevent CRC-related deaths. The present article aims to summarize the most recent findings concerning the use of either genetic or epigenetic (mainly related to DNA methylation) biomarkers for CRC diagnosis, prognosis, and response to treatment. Recent large-scale DNA methylation studies suggest that CRC can be divided into several subtypes according to the frequency of DNA methylation and those of mutations in key CRC genes, and that this is reflected by different prognostic outcomes. Increasing evidence suggests that the analysis of DNA methylation in blood or fecal specimens could represent a valuable non-invasive diagnostic tool for CRC. Moreover, a broad spectrum of studies indicates that the inter-individual response to chemotherapeutic treatments depends on both epigenetic modifications and genetic mutations occurring in colorectal cancer cells, thereby opening the way for a personalized medicine. Overall, combining genetic and epigenetic data might represent the most promising tool for a proper diagnostic, prognostic and therapeutic approach.
| S-EPMC3921546 | biostudies-literature
Project description:Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. One of the fundamental processes driving the initiation and progression of CRC is the accumulation of a variety of genetic and epigenetic changes in colonic epithelial cells. Over the past decade, major advances have been made in our understanding of cancer epigenetics, particularly regarding aberrant DNA methylation, microRNA (miRNA) and noncoding RNA deregulation, and alterations in histone modification states. Assessment of the colon cancer "epigenome" has revealed that virtually all CRCs have aberrantly methylated genes and altered miRNA expression. The average CRC methylome has hundreds to thousands of abnormally methylated genes and dozens of altered miRNAs. As with gene mutations in the cancer genome, a subset of these epigenetic alterations, called driver events, are presumed to have a functional role in CRC. In addition, the advances in our understanding of epigenetic alterations in CRC have led to these alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC.
| S-EPMC4589488 | biostudies-literature
Project description:Colorectal cancer (CRC) arise from multi-step carcinogenesis due to genetic mutations and epigenetic modifications of human genome. Genetic mutations and epigenetic modifications were originally established as 2 independent mechanisms contributing to colorectal carcinogenesis. However, recent evidences demonstrate that there are interactions between these 2 mechanisms. Genetic mutations enable disruption of epigenetic controls while epigenetic modifications can initiate genomic instability and carcinogenesis. This review summarized genetic mutations and epigenetic modifications in colorectal carcinogenesis and molecular classification of CRC subtype based on genetic or epigenetic biomarkers for treatment response and prognosis. Molecular subtypes of CRC will permit the implementation of precision medicine with better outcome of management for CRC.
| S-EPMC6077299 | biostudies-literature
Project description:MicroRNAs (miRNAs) are one abundant class of small, endogenous non-coding RNAs, which regulate various biological processes by inhibiting expression of target genes. miRNAs have important functional roles in carcinogenesis and development of colorectal cancer (CRC), and emerging evidence has indicated the feasibility of miRNAs as robust cancer biomarkers. This review summarizes the progress in miRNA-related research, including study of its oncogene or tumour-suppressor roles and the advantages of miRNA biomarkers for CRC diagnosis, treatment and recurrence prediction. Along with analytical technique improvements in miRNA research, use of the emerging extracellular miRNAs is feasible for CRC diagnosis and prognosis.
| S-EPMC6367136 | biostudies-literature
Project description:Ovarian cancer ranks the most lethal among gynecologic neoplasms in women. To develop potential biomarkers for diagnosis, we have identified five novel genes (CYP39A1, GTF2A1, FOXD4L4, EBP, and HAAO) that are hypermethylated in ovarian tumors, compared with the non-malignant normal ovarian surface epithelia, using the quantitative methylation-specific polymerase chain reactions. Interestingly enough, multivariate Cox regression analysis has identified hypermethylation of CYP39A1 correlated with an increase rate of relapsing (P=0.032, hazard ratio >1). Concordant hypermethylation in at least three loci was observed in 50 out of 55 (91%) of ovarian tumors examined. The test sensitivity and specificity were assessed to be 96 and 67% for CYP39A1; 95 and 88% for GTF2A1; 93 and 67% for FOXD4L4; 81 and 67% for EBP; 89 and 82% for HAAO, respectively. Our data have identified, for the first time, GTF2A1 alone, or GTF2A1 plus HAAO are excellent candidate biomarkers for detecting this disease. Moreover, the known functions of these gene products further implicate dysregulated transcriptional control, cholesterol metabolism, or synthesis of quinolinic acids, may play important roles in attributing to ovarian neoplasm. Molecular therapies, by reversing the aberrant epigenomes using inhibitory agents or by abrogating the upstream signaling pathways that convey the epigenomic perturbations, may be developed into promising treatment regimens.
| S-EPMC2829240 | biostudies-literature
Project description:BACKGROUND:The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence. METHODS:Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched-chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc-finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold). RESULTS:The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%-69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%-36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%-99.6%; CEA, 96.4%; 95% CI, 91.4%-99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9-1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3-20.6; P = .407). CONCLUSIONS:The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.
| S-EPMC7155014 | biostudies-literature
Project description:Lung cancer is the leading cause of human cancer mortality due to the lack of early diagnosis technology. The low-dose computed tomography scan (LDCT) is one of the main techniques to screen cancers. However, LDCT still has a risk of radiation exposure and it is not suitable for the general public. In this study, plasma metabolic profiles of lung cancer were performed using a comprehensive metabolomic method with different liquid chromatography methods coupled with a Q-Exactive high-resolution mass spectrometer. Metabolites with different polarities (amino acids, fatty acids, and acylcarnitines) can be detected and identified as differential metabolites of lung cancer in small volumes of plasma. Logistic regression models were further developed to identify cancer stages and types using those significant biomarkers. Using the Variable Importance in Projection (VIP) and the area under the curve (AUC) scores, we have successfully identified the top 5, 10, and 20 metabolites that can be used to differentiate lung cancer stages and types. The discrimination accuracy and AUC score can be as high as 0.829 and 0.869 using the five most significant metabolites. This study demonstrated that using 5 + metabolites (Palmitic acid, Heptadecanoic acid, 4-Oxoproline, Tridecanoic acid, Ornithine, and etc.) has the potential for early lung cancer screening. This finding is useful for transferring the diagnostic technology onto a point-of-care device for lung cancer diagnosis and prognosis.
| S-EPMC8175557 | biostudies-literature
Project description:Detection of DNA hypermethylation has emerged as a novel molecular biomarker for the evaluation of prostate cancer diagnosis and prognosis, but the use of single gene hypermethylation could produce unspecific results. Defining the specific gene hypermethylation profile for prostate cancer could provide groups of genes that specifically discriminate the patients with indolent and aggressive tumors. To compare the methylation profile of normal and malignant prostate we performed Genome-wide methylation analysis on 83 tumor samples, that included all clinical stages of the disease, 10 normal prostate samples and LNCaP, DU145 and PC3 prostate cancer cell lines using the GoldenGate Methylation Cancer Panel I (Illumina, Inc.) that interrogate for 1505 CpGs. We found 41 genes significantly hypermethylated in more than 20% of the tumors analyzed (p<0.01). Of these we identified GSTM2 and PENK as novel hypermethylated genes in prostate cancer that were simultaneously methylated in 40.9% of the tumors analyzed. We also identified panels of genes more frequently methylated in tumor samples with clinico-pathological indicators of poor prognosis: high Gleason score, elevated Ki-67 or advanced disease. Of these, we found that simultaneous hypermethylation of CFTR and HTR1B is common in patients with high Gleason score and high ki-67 levels and might signal the population at higher risk of therapeutic failure. DNA hypermethylation profile was associated with cancer-specific mortality (log-rank, p=0.007) and biochemical recurrence-free survival (log-rank, p=0.0008). In conclusion, our data strongly indicate that epigenetic silencing of GSTM2 and PENK is a common event in prostate cancer that could be used as a molecular marker for prostate cancer diagnosis. In addition, simultaneous HTR1B and CFTR hypermethylation could help discriminate aggressive from indolent prostate tumors.A DNA hypermethylation profile associated with cancer-specific mortality and biochemical recurrence in patients receiving radical prostatectomy is presented. GST2 and PENK are new hipermethylated genes identified. Simultaneous hypermethylation of CFTR and HTR1B could help discriminate aggressive disease.
2014-12-31 | GSE46177 | GEO
Project description:Colorectal cancer is a major health burden, and a leading cause of cancer-related deaths in industrialized countries. The steady improvements in surgery and chemotherapy have improved survival, but the ability to identify high- and low-risk patients is still somewhat poor. Molecular biology has, over the years, given insight into basic principles of colorectal cancer initiation and development. These findings include aberrations increasing risk of tumor development, genetic changes associated with the stepwise progression of the disease, and errors predicting response to a specific treatment. Potential biomarkers in colorectal cancer are extensively studied, and how the molecular aberrations relate to clinical features. Yet, little of this knowledge has been possible to transfer into clinical practice. In this review, an overview of colorectal cancer genetics will be given, as well as how aberrations found in this tumor type are proposed as biomarkers for risk prediction, as diagnostic tools, for prognosis or prediction of treatment outcome.
| S-EPMC3257138 | biostudies-literature
Project description:Gastric cancer is one of leading causes of cancer-related mortality worldwide and is a notable disease due to its heterogeneity. Recently, numerous studies have investigated the molecular basis of gastric cancer, involving the alteration of pathogenesis, and invasion and metastasis. With the development of modern technologies, various novel biomarkers had been identified that appear to possess diagnostic and prognostic value; therefore, the present review describes our current knowledge of biomarkers for the early diagnosis and prognosis of gastric cancer. Classic biomarkers for gastric cancer diagnosis include carcinoembryonic antigen and cancer antigen 19-9, while microRNA and DNA hypomethylation are proposed as novel biomarkers. Excluding classical biomarkers, biomarkers for determining the progression and prognosis of gastric cancer focus on targeting microRNAs, epigenetic alterations and genetic polymorphisms.
| S-EPMC4356326 | biostudies-literature