scholarly journals Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Christina Michailidi ◽  
Ethan Soudry ◽  
Mariana Brait ◽  
Leonel Maldonado ◽  
Andrew Jaffe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Promoter Hypermethylation ◽  
Basic Requirement ◽  
Dna Hypomethylation ◽  
Oligonucleotide Arrays ◽  
Tiling Arrays ◽  
Specific Pcr ◽  
Genome Wide ◽  
Methylation Peak

The majority of the epigenomic reports in hepatocellular carcinoma have focused on identifying novel differentially methylated drivers or passengers of the oncogenic process. Few reports have considered the technologies in place for clinical translation of newly identified biomarkers. The aim of this study was to identify epigenomic technologies that need only a small number of samples to discriminate HCC from non-HCC tissue, a basic requirement for biomarker development trials. To assess that potential, we used quantitative Methylation Specific PCR, oligonucleotide tiling arrays, and Methylation BeadChip assays. Concurrent global DNA hypomethylation, gene-specific hypermethylation, and chromatin alterations were observed as a hallmark of HCC. A global loss of promoter methylation was observed in HCC with the Illumina BeadChip assays and the Nimblegen oligonucleotide arrays. HCC samples had lower median methylation peak scores and a reduced number of significant promoter-wide methylated probes. Promoter hypermethylation ofRASSF1A,SSBP2, andB4GALT1quantified by qMSP had a sensitivity ranging from 38% to 52%, a specificity of 100%, and an AUC from 0.58 to 0.75. A panel combining these genes with HCC risk factors had a sensitivity of 87%, a specificity of 100%, and an AUC of 0.91.

scholarly journals SOMATOSTATIN (SST) PROMOTER HYPERMETHYLATION IN ASSOCIATION WITH COLORECTAL CANCER

2020 ◽  
Vol 17 (36) ◽  
pp. 1075-1082
Author(s):  
Mohammed FAWZI ◽  
Ahmed TAIFI ◽  
Zahraa Kamil Kadhim LAWI
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Cancer Progression ◽  
Early Stage ◽  
Promoter Hypermethylation ◽  
Healthy Controls ◽  
Dna Hypermethylation ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Common Diagnosis

Colorectal cancer (CRC) is one of the most common diagnosis malignancies with different risk factors, including environmental and genetic. Several genes, called tumor suppressor genes, play an essential role in inhibiting these risk factors by preventing tumor development. One of these genes is somatostatin (SST). Somatostatin is an antiproliferative peptide with pro-apoptotic effects that enhance cell death to prevent tumor growth. This study aimed to investigate the association relationship between DNA methylation in SST promotor and colorectal cancer progression. After DNA bisulfite conversion, SST promoter methylation was examined using quantitative methylation‐specific PCR (qMSP) in 71 cases (19 metastasis CRC, 28 early-stage CRC, and 24 healthy controls). Quantitative methylation‐specific PCR (qMSP) is a real-time PCR method used to determine the unmethylated and methylated cytosine residues using a specific set of primers. The percentage of hypermethylation in SST promoter was 17%, 60%, and 79% for healthy controls, early-stage, and metastasis CRC groups. The results showed a significant association between DNA hypermethylation of SST promoter and CRC progression. P-values were 0.0364 for the early-stage group and 0.0138 for the metastasis group. The results also supported that the DNA hypermethylation block the expression of SST, which in turn induce carcinogenesis. The detection of SST promoter hypermethylation at early stage of cancer could be used as a biomarker for screening and prognosis of CRC.

scholarly journals Promoter hypermethylation in MLL-r infant acute lymphoblastic leukemia: biology and therapeutic targeting

Blood ◽  
2010 ◽  
Vol 115 (23) ◽  
pp. 4798-4809 ◽  
Author(s):  
Eric Schafer ◽  
Rafael Irizarry ◽  
Sandeep Negi ◽  
Emily McIntyre ◽  
Donald Small ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Dna Methyltransferase ◽  
Cpg Island ◽  
Lymphoblastic Leukemia ◽  
Promoter Hypermethylation ◽  
Therapeutic Targeting ◽  
Specific Pcr ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Infant Acute Lymphoblastic Leukemia

Abstract Cooperating leukemogenic events in MLL-rearranged (MLL-r) infant acute lymphoblastic leukemia (ALL) are largely unknown. We explored the role of promoter CpG island hypermethylation in the biology and therapeutic targeting of MLL-r infant ALL. The HELP (HpaII tiny fragment enrichment by ligation-mediated polymerase chain reaction [PCR]) assay was used to examine genome-wide methylation of a cohort of MLL-r infant leukemia samples (n = 5), other common childhood ALLs (n = 5), and normals (n = 5). Unsupervised analysis showed tight clustering of samples into their known biologic groups, indicating large differences in methylation patterns. Global hypermethylation was seen in the MLL-r cohort compared with both the normals and the others, with ratios of significantly (P < .001) hypermethylated to hypomethylated CpGs of 1.7 and 2.9, respectively. A subset of 7 differentially hypermethylated genes was assayed by quantitative reverse-transcription (qRT)–PCR, confirming relative silencing in 5 of 7. In cell line treatment assays with the DNA methyltransferase inhibitor (DNMTi) decitabine, MLL-r (but not MLL wild-type cell lines) showed dose- and time-dependent cytotoxicity and re-expression of 4 of the 5 silenced genes. Methylation-specific PCR (MSP) confirmed promoter hypermethylation at baseline, and a relative decrease in methylation after treatment. DNMTi may represent a novel molecularly targeted therapy for MLL-r infant ALL.

Risk Factors for Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt in Patients with Hepatocellular Carcinoma and Portal Hypertension

2015 ◽  
Vol 24 (3) ◽  
pp. 301-307 ◽  
Author(s):  
Jiannan Yao ◽  
Li Zuo ◽  
Guangyu An ◽  
Zhendong Yue ◽  
Hongwei Zhao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Portal Hypertension ◽  
Hepatic Encephalopathy ◽  
Pressure Gradient ◽  
Transjugular Intrahepatic Portosystemic Shunt ◽  
Meld Score ◽  
Portosystemic Shunt ◽  
Portal Flow ◽  
Intrahepatic Portosystemic Shunt

Aims: This study aimed at assessing the risk factors for hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with hepatocellular carcinoma (HCC) and portal hypertension. Method: Consecutive patients (n=279) with primary HCC who underwent TIPS between January 1997 and March 2012 at a single institution were retrospectively reviewed. Patients were followed up for 2 years. Pre-TIPS, peri-TIPS and post-TIPS clinical variables were reviewed using univariate and multivariate analyses to identify risk factors for HE after TIPS. Results: The overall incidence of HE was 41% (114/279). Multivariate analysis showed an increased odds for HE in patients with: >3 treatments with transcatheter arterial chemoembolization (TACE) and/or trans-arterial embolization (TAE) (odds ratio [OR], 4.078; 95% confidence interval [95%CI], 1.748-9.515); hepatopetal portal flow (OR, 2.362; 95%CI, 1.032-5.404); high portosystemic pressure gradient (OR, 1.198; 95%CI, 1.073-1.336) and high pre-TIPS MELD score (OR, 1.693; 95%CI, 1.390-2.062). Odds for HE were increased 1.693 fold for each 1-point increase in the MELD score, and 1.198 fold for each 1-mmHg decrease in the post-TIPS portosystemic pressure gradient. Conclusion: The identification of clinical variables associated with increased odds of HE may be useful for the selection of appropriate candidates for TIPS. Results suggest that an inappropriate decrease in the portosystemic pressure gradient might be associated with HE after TIPS. In addition, >3 treatments with TACE/TAE, hepatopetal portal flow, and high MELD score were also associated with increased odds of HE after TIPS. Key words:  –  –  – .

P6017 A high density genome-wide scan for genetic risk factors of insect bite hypersensitivity (IBH): A Horsegene Project Initiative

2016 ◽  
Vol 94 (suppl_4) ◽  
pp. 156-157
Author(s):  
B. D. Velie ◽  
M. Shrestha ◽  
L. Francois ◽  
A. Schurink ◽  
A. Stinckens ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
High Density ◽  
Genome Wide ◽  
Insect Bite Hypersensitivity ◽  
Genome Wide Scan

scholarly journals Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Jing-dong Zhou ◽  
Ting-juan Zhang ◽  
Zi-jun Xu ◽  
Zhao-qun Deng ◽  
Yu Gu ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Myelodysplastic Syndromes ◽  
Bisulfite Sequencing ◽  
De Novo ◽  
Dna Hypermethylation ◽  
Reduced Representation ◽  
Targeted Bisulfite Sequencing ◽  
Specific Pcr ◽  
Genome Wide ◽  
Potential Biomarker

AbstractThe potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.

scholarly journals Racial Differences in Hepatocellular Carcinoma Incidence and Risk Factors among a Low Socioeconomic Population

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3710
Author(s):  
Sylvie Muhimpundu ◽  
Rebecca Baqiyyah N. Conway ◽  
Shaneda Warren Andersen ◽  
Loren Lipworth ◽  
Mark D. Steinwandel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Cohort Study ◽  
African Americans ◽  
Racial Differences ◽  
Prospective Cohort ◽  
White Americans ◽  
Low Socioeconomic ◽  
Factors Associated ◽  
Southeastern Us

The purpose of this study was to examine differences in risk factors associated with hepatocellular carcinoma (HCC) among White and African Americans from low socioeconomic backgrounds in the Southern Community Cohort Study (SCCS). The SCCS is a prospective cohort study with participants from the southeastern US. HCC incidence rates were calculated. Multivariable Cox regression was used to calculate HCC-adjusted hazard ratios (aHR) associated with known baseline HCC risk factors for White and African Americans, separately. There were 294 incident HCC. The incidence rate ratio for HCC was higher (IRR = 1.4, 95%CI: 1.1–1.9) in African Americans compared to White Americans. White Americans saw a stronger association between self-reported hepatitis C virus (aHR = 19.24, 95%CI: 10.58–35.00) and diabetes (aHR = 3.55, 95%CI: 1.96–6.43) for the development of HCC compared to African Americans (aHR = 7.73, 95%CI: 5.71–10.47 and aHR = 1.48, 95%CI: 1.06–2.06, respectively) even though the prevalence of these risk factors was similar between races. Smoking (aHR = 2.91, 95%CI: 1.87–4.52) and heavy alcohol consumption (aHR = 1.59, 95%CI: 1.19–2.11) were significantly associated with HCC risk among African Americans only. In this large prospective cohort, we observed racial differences in HCC incidence and risk factors associated with HCC among White and African Americans.

scholarly journals Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1023
Author(s):  
Eirini I. Rigopoulou ◽  
George N. Dalekos
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Diseases ◽  
Treatment Modalities ◽  
Primary Biliary Cholangitis ◽  
Autoimmune Liver Diseases ◽  
Increased Risk ◽  
Liver Cancers ◽  
Medium Risk ◽  
Causes Of Mortality

Hepatocellular carcinoma (HCC), the commonest among liver cancers, is one of the leading causes of mortality among malignancies worldwide. Several reports demonstrate autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) to confer increased risk of hepatobiliary malignancies, albeit at lower frequencies compared to other liver diseases. Several parameters have been recognized as risk factors for HCC development in AIH and PBC, including demographics such as older age and male sex, clinical features, the most decisive being cirrhosis and other co-existing factors, such as alcohol consumption. Moreover, biochemical activity and treatment response have been increasingly recognized as prognostic factors for HCC development in AIH and PBC. As available treatment modalities are effective only when HCC diagnosis is established early, surveillance has been proven essential for HCC prognosis. Considering that the risk for HCC is not uniform between and within disease groups, refinement of screening strategies according to prevailing demographic, clinical, and molecular risk factors is mandated in AILDs patients, as personalized HCC risk prediction will offer significant advantage in patients at high and/or medium risk. Furthermore, future investigations should draw attention to whether modification of immunosuppression could benefit AIH patients after HCC diagnosis.

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