Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined whether TFPI2 methylation can be used as a molecular marker for colorectal cancers by detecting TFPI2 methylation in colorectal cancer patients' sera by using quantitative methylation-specific polymerase chain reaction (qMSP). The qMSP analysis showed that 39 of 215 (18%) patients exhibited TFPI2 methylation in their serum DNA, suggesting that TFPI2 methylation frequently existed in colorectal cancer patients' sera. After completion of qMSP analysis, clinicopathological data were correlated with molecular data. TFPI2 methylation was significant in the sera of patients with large (p = 0.0022), poorly differentiated carcinoma (p = 0.0164), deep invasion (p = 0.0002), lymph node metastasis (p = 0.0147), or distant metastasis (p < 0.0001). Moreover, TFPI2 methylation was observed more frequently according to the progression of TNM stage, suggesting that serum TFPI2 methylation could be detected more easily in patients with advanced colorectal cancer. We also examined whether serum TFPI2 methylation would be useful in the detection of colorectal cancer, compared to the conventional tumor markers. Detection rates of colorectal cancer using the tumor markers TFPI2 methylation, CEA and CA19-9, in the serum were 18%, 33%, and 17%, respectively. In cases where we combined all three markers, the detection rate was 42%. High sensitivity of qMSP enables detection of smaller amounts of serum tumor DNA. In principle, the methylation status of a primary tumor is not required in advance to detect circulating tumor DNA, suggesting the potential of qMSP as a cancer screening method.
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PMID:Detection of TFPI2 methylation in the serum of colorectal cancer patients. 2182 Jul 98

CpG Island Methylator Phenotype (CIMP) is one of the underlying mechanisms in colorectal cancer (CRC). This study aimed to define a methylome signature in CRC through a methylation microarray analysis and a compilation of promising CIMP markers from the literature. Illumina HumanMethylation27 (IHM27) array data was generated and analyzed based on statistical differences in methylation data (1st approach) or based on overall differences in methylation percentages using lower 95% CI (2nd approach). Pyrosequencing was performed for the validation of nine genes. A meta-analysis was used to identify CIMP and non-CIMP markers that were hypermethylated in CRC but did not yet make it to the CIMP genes' list. Our 1st approach for array data analysis demonstrated the limitations in selecting genes for further validation, highlighting the need for the 2nd bioinformatics approach to adequately select genes with differential aberrant methylation. A more comprehensive list, which included non-CIMP genes, such as APC, EVL, CD109, PTEN, TWIST1, DCC, PTPRD, SFRP1, ICAM5, RASSF1A, EYA4, 30ST2, LAMA1, KCNQ5, ADHEF1, and TFPI2, was established. Array data are useful to categorize and cluster colonic lesions based on their global methylation profiles; however, its usefulness in identifying robust methylation markers is limited and rely on the data analysis method. We have identified 16 non-CIMP-panel genes for which we provide rationale for inclusion in a more comprehensive characterization of CIMP+ CRCs. The identification of a definitive list for methylome specific genes in CRC will contribute to better clinical management of CRC patients.
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PMID:Toward a comprehensive and systematic methylome signature in colorectal cancers. 2397 90

The fecal occult blood test (FOBT) is widely used for colorectal cancer (CRC) screening to reduce the mortality rate associated with this cancer. However, several problems exist, as FOBT results can contain some false-negative CRC patients and some-false positive healthy subjects. Thus, to resolve these problems, several fecal biomarkers based on fecal protein, fecal DNA, and fecal RNA have been reported. Fecal calprotectin, which indicates intestinal bleeding or inflammation of the colon mucosa, and fecal tumor M2-PK, which is produced by cancer cells, have been extensively investigated as fecal protein biomarkers. To detect small amounts of CRC-specific proteins, the chemiluminescent enzyme immunoassay (CLEIA), which is a highly sensitive protein detection method using immunomagnetic beads, will be used. DNA mutation of APC, KRAS, and TP53 genes and DNA methylation of VIM, TFPI2, BMP3, NDRG4, and SFRP2 genes were reported as fecal DNA biomarkers. Consequently, a fecal DNA test named Cologuard from Exact Sciences was approved by the FDA in August 2014. Fecal COX2, MMP7, miR-106a, miR-92a, and miR-223 were also reported as fecal RNA biomarkers. This review article summarizes fecal biomarkers using fecal samples for CRC diagnosis.
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PMID:[Fecal Biomarker for Colorectal Cancer Diagnosis]. 2652 59

Recently, 5-hydroxymethylcytosine patterning across the tumor genome was considered as a hallmark of cancer development and progression. However, locus-specific difference of hydroxymethylation between colorectal cancer and normal tissue is unknown. In this study, we performed a newly developed method, HMST-seq, to profile 726 aberrant methylated loci and 689 aberrant hydroxymethylated loci synchronously in genome wide of colorectal cancers, majority of which presented higher methylation or lower hydroxymethylationin than in normal group. Besides, abnormal hydroxymethylated modification was more frequently occur at proximal regions close to TSSs and TSSs regions than abnormal methylation. Subsequently, we screened four genes (ALOX15, GHRHR, TFPI2 and TKTL1) with aberrant methylation and aberrant hydroxymethylation at some genome position by functional enrichment analysis as candidate genes associated with colorectal cancer. Our results may allow us to select differentially epigenetically modified target genes implicated in colorectal cancer tumorigenesis.
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PMID:Filtrating colorectal cancer associated genes by integrated analyses of global DNA methylation and hydroxymethylation in cancer and normal tissue. 2754 20

Gastrointestinal cancer is a prevalent disease with high morbidity and mortality. Tissue factor pathway inhibitor 2 (TFPI2) gene could protect the extracellular matrix of cancer cells from degradation and tumor invasion. The goal of our study was to estimate the diagnostic value of TFPI2 hypermethylation in gastric cancer (GC) and colorectal cancer (CRC). TFPI2 methylation was measured by quantitative methylation-specific polymerase chain reaction (qMSP) method in 114 GC and 80 CRC tissues and their paired non-tumor tissues. Our results showed that TFPI2 methylation was significantly higher in tumor tissues (GC: 29.940% vs. 12.785%, P < 0.001; CRC: 26.930% vs. 5.420%, P < 0.001). The methylation level of TFPI2 in colorectal tumor tissues was significantly higher than that in colorectal normal tissues (26.930% versus 0.002%, P < 0.00001). In GC, TFPI2 hypermethylation yielded an area under the curve (AUC) of 0.762 (95% CI: 0.696-0.828) with a sensitivity of 68% and a specificity of 83%. In CRC, TFPI2 hypermethylation yielded an AUC of 0.759 (95% CI: 0.685-0.834) with a sensitivity of 61% and a specificity of 84%. Similarly, TCGA data also supported TFPI2 hypermethylation was a promising diagnostic marker for GC and CRC. Moreover, the dual-luciferase reporter assay showed TFPI2 fragment could upregulate gene expression (fold change = 5, P = 0.005). Data mining further indicated that TFPI2 expression in CRC cell lines was significantly increased after 5'-AZA-deoxycytidine treatment (fold change > 1.37). In conclusion, TFPI2 hypermethylation might be a promising diagnostic biomarker for GC and CRC.
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PMID:The role of TFPI2 hypermethylation in the detection of gastric and colorectal cancer. 2913 4

Recently, nuclear poly-ADP-ribosylation had aroused research interest in epigenetics, but little attempt to explore functions of mono-ADP-ribosylation of histone, the major formation of histone ADP-ribosylated modification. We have previously reported a novel mono-ADP-ribosylation of H3R117, which promoted proliferation of LoVo cells. Here we showed that mono-ADP-ribosylated H3R117 of LoVo cells depressed demethylation of tumor suppressor TFPI2 promoter by suppressing TET1 expression and adjusting H3K9me3 enrichment of TFPI2 promoter to attenuate affinity of TET1, besides, since high H3K27me3 level was associated with hypermethylation, mono-ADP-ribosylated-H3R117-depended-H3K27me3 of TFPI2 promoter may contribute to hypermethylation of TFPI2. However, H3R117A mutation increased poly-ADP-ribosylated modification of TET1 promoter not TFPI2 promoter, which resulted in boosting transcription and expression of TET1 by altering DNA methylated modification, chromatin accessibility, and histone-methylated modification of TET1 promoter, while knockout TET1 of H3R117A LoVo cells directly led to hypermethylation of TFPI2 promoter and depression of TFPI2 secretion as well as enhanced proliferation, suggested that TET1 played a key role in demethylation of TFPI2, production of TFPI2, and cell proliferation. Bioinformatics analyses reveal prevalent hypermethylation of TFPI2 was an early event in tumorigenesis of colorectal caner, and expression of TET1 and TFPI2 was positive correlation in colorectal cancer and normal tissue. These data suggested that mono-ADP-ribosylation of H3R117 upregulated methylation of TFPI2 by impact TET1, since hypermethyaltion of TFPI2 was an early event in tumorigenesis, selectively target mono-ADP-ribosylation of H3R117 deficiency could be a feasible way to block tumorigenesis of colorectal cancer.
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PMID:Mono-ADP-ribosylation of H3R117 traps 5mC hydroxylase TET1 to impair demethylation of tumor suppressor gene TFPI2. 3065 99

Colorectal cancer (CRC) arises from accumulated genetic and epigenetic alterations, which provide the possibility to identify tumor-specific biomarkers by analyzing fecal DNA. Methylation status in human genes from tumor tissue is highlighted as promising biomarker in the early detection of CRC. A number of studies have documented altered methylation levels in DNA extracted from stool samples, but generated heterogeneous results. We performed a systematic review and quantitative assessment of existing studies to compare levels of DNA methylation in most frequently studied genes and their diagnostic value in CRC and its precursor, colorectal adenoma, with their counterparts in healthy subjects. Robust searches of the literature were performed in our study with explicit strategies and definite inclusion/exclusion criteria. Pooled data revealed that methylation levels of SFRP2, SFRP1, TFPI2, BMP3, NDRG4, SPG20, and BMP3 plus NDRG4 genes exceeded a sensitivity of 70% and a specificity of 80% for CRC detection. The DOR of the seven candidate biomarkers ranged from 19.80 to 334.33, indicating a good diagnostic power in discriminating cancer from normal tissues. The AUC range was from 0.88 to 0.95, indicating a good or very good discriminatory performance. When test results for BMP3 and NDRG4 were combined, the DOR of CRC detection was 98.36, which was higher than that for BMP3 and NDRG4 separately. As for adenoma detection, the DOR of methylated NDRG4 is higher than that for CRC (CRC vs. adenoma: 54.86 vs. 57.22). Both the sensitivity and specificity of NDRG4 for adenoma detection exceeded 70%. These findings demonstrate the eligibility and feasibility of DNA methylation as a minimally invasive biomarker in feces in the diagnosis of CRC and adenoma. The use of DNA from human stools has the potential to be readily applicable to detect aberrant DNA methylation levels among many subjects for CRC early screening.
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PMID:A systematic review and quantitative assessment of methylation biomarkers in fecal DNA and colorectal cancer and its precursor, colorectal adenoma. 3109 51