scholarly journals An analysis about heterogeneity among cancers based on the DNA Methylation Patterns

2019 ◽  
Author(s):  
Yang Liu ◽  
Yue Gu ◽  
Mu Su ◽  
Hui Liu ◽  
Shumei Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Survival Analysis ◽  
Environmental Factors ◽  
Prognostic Markers ◽  
Cox Regression ◽  
Regulation Of Gene Expression ◽  
Absolute Difference ◽  
Marker Genes ◽  
Gene Markers ◽  
Significant Difference

Abstract Background: The occurrence of cancer is usually the result of a co-effect of genetic and environmental factors. It is generally believed that the main cause of cancer is the accumulation of genetic mutations, and DNA methylation, as one of the epigenetic modifications closely related to environmental factors, participates in the regulation of gene expression and cell differentiation and plays an important role in the development of cancer. Methods: This article discusses the epigenetic heterogeneity of cancer in detail. Firstly DNA methylation data of 7 cancer types were obtained from Illumina Infinium HumanMethylation 450K platform of TCGA database. Diagnostic markers of each cancer were obtained by t-test and absolute difference of DNA differencial methylation analysis. Enrichment analysis of these specific markers indicated that they were involved in different biological functions. Secondly, important gene markers were obtained by constructing the DNA methylation correlation network and the gene interaction network in the KEGG pathway, and 317 marker genes set obtained from two networks were integrated as candidate markers for the prognosis model. The univariate and multivariate COX regression models were used to select specific independent prognostic markers for each cancer, and a risk-score model was constructed to divide patients of each cancer into two groups, highly-risky and lowly-risky groups. Results: Kaplan-Meier survival analysis showed that there was significant difference in survival between the two groups. In the verification set, there was also a difference in survival between the highly and lowly risky groups. Conclusions: This study screened out reliable prognostic markers for different cancers, providing a further explanation for the heterogeneity of cancer at the DNA methylation level and more targets for clinical conversion studies of cancer. Kewords: DNA methylation; cancer; epigenetic heterogeneity; survival analysis

scholarly journals An analysis about heterogeneity among cancers based on the DNA methylation patterns

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Liu ◽  
Yue Gu ◽  
Mu Su ◽  
Hui Liu ◽  
Shumei Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Survival Analysis ◽  
Prognostic Markers ◽  
Differential Methylation ◽  
Specific Gene ◽  
Cancer Type ◽  
Methylation Analysis ◽  
Gene Markers ◽  
Significant Difference ◽  
Differential Methylation Analysis

Abstract Background It is generally believed that DNA methylation, as one of the most important epigenetic modifications, participates in the regulation of gene expression and plays an important role in the development of cancer, and there exits epigenetic heterogeneity among cancers. Therefore, this study tried to screen for reliable prognostic markers for different cancers, providing further explanation for the heterogeneity of cancers, and more targets for clinical transformation studies of cancer from epigenetic perspective. Methods This article discusses the epigenetic heterogeneity of cancer in detail. Firstly, DNA methylation data of seven cancer types were obtained from Illumina Infinium HumanMethylation 450 K platform of TCGA database. Then, differential methylation analysis was performed in the promotor region. Secondly, pivotal gene markers were obtained by constructing the DNA methylation correlation network and the gene interaction network in the KEGG pathway, and 317 marker genes obtained from two networks were integrated as candidate markers for the prognosis model. Finally, we used the univariate and multivariate COX regression models to select specific independent prognostic markers for each cancer, and studied the risk factor of these genes by doing survival analysis. Results First, the cancer type-specific gene markers were obtained by differential methylation analysis and they were found to be involved in different biological functions by enrichment analysis. Moreover, specific and common diagnostic markers for each type of cancer was sorted out and Kaplan-Meier survival analysis showed that there was significant difference in survival between the two risk groups. Conclusions This study screened out reliable prognostic markers for different cancers, providing a further explanation for the heterogeneity of cancer at the DNA methylation level and more targets for clinical conversion studies of cancer.

scholarly journals Constructing the Logical Regression Model to Predict the Target of Jianpi Jiedu Decoction in the Treatment of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rongjie Zhang ◽  
Yan Chen ◽  
Ge Zhou ◽  
Baoguo Sun ◽  
Yue Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Regression Model ◽  
Target Genes ◽  
Cox Regression ◽  
Risk Group ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Prognostic Analysis ◽  
Significant Difference

Objectives. The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods. The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results. 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group ( p < 0.05 ). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues ( p < 0.05 ). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC ( p < 0.05 ). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions. In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1.

scholarly journals Head and neck cutaneous melanoma: 5-year survival analysis in a Serbian university center

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Aleksandar Višnjić ◽  
Predrag Kovačević ◽  
Asen Veličkov ◽  
Mariola Stojanović ◽  
Stefan Mladenović
Keyword(s):  
Survival Analysis ◽  
Head And Neck ◽  
Cutaneous Melanoma ◽  
Cox Regression ◽  
Total Sample ◽  
Advanced Stage ◽  
Cross Sectional ◽  
Cox Regression Analysis ◽  
Significant Difference

Abstract Background Head and neck melanoma (HNM) is specific from the anatomical and etiopathogenetic aspects. In addition to morphopathological parameters, rich vascularization and lymphatic drainage of the head and neck affect the occurrence of lymphogenic and hematogenous metastases, as well as the metastases on both sides of the neck. Methods A retrospective cross-sectional study included cutaneous melanoma patients who underwent surgery at a clinical center over a 10-year period. The clinical follow-up was at least 60 months. The Kaplan-Meier method was used for the survival analysis. The predictor effect of certain independent variables on a given dichotomous dependent variable (survival) was measured by the Cox regression analysis. Results The analysis of demographic and clinical characteristics of 116 patients with HNM revealed that there was no statistically significant difference in age and gender in the total sample. Thirty-three (28.45%) patients were already in stage III or IV of the disease at the first examination, which affected the overall survival rate. The overall 5-year survival was 30.2%. No statistically significant difference in 5-year survival was found in relation to age and location. The period without melanoma progression decreased progressively in the advanced stage. Forty-nine patients (42%) underwent surgery for lymphogenic metastases in the parotid region and/or neck during the follow-up. Conclusions Patients with HNM included in this study frequently presented an advanced stage of the disease at the first examination, which is reflected in a low rate of 5-year survival. Early diagnosis and adequate primary treatment can ensure longer survival.

scholarly journals Integrative analysis of DNA methylation and gene expression identified cervical cancer-specific diagnostic biomarkers

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Wanxue Xu ◽  
Mengyao Xu ◽  
Longlong Wang ◽  
Wei Zhou ◽  
Rong Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Dna Methylation ◽  
Regulation Of Gene Expression ◽  
Cervical Squamous Cell Carcinoma ◽  
Integrative Analysis ◽  
Machine Learning Techniques ◽  
Marker Genes ◽  
Normal Tissues ◽  
Candidate Set

AbstractCervical cancer is the leading cause of death among women with cancer worldwide. Here, we performed an integrative analysis of Illumina HumanMethylation450K and RNA-seq data from TCGA to identify cervical cancer-specific DNA methylation markers. We first identified differentially methylated and expressed genes and examined the correlation between DNA methylation and gene expression. The DNA methylation profiles of 12 types of cancers, including cervical cancer, were used to generate a candidate set, and machine-learning techniques were adopted to define the final cervical cancer-specific markers in the candidate set. Then, we assessed the protein levels of marker genes by immunohistochemistry by using tissue arrays containing 93 human cervical squamous cell carcinoma samples and cancer-adjacent normal tissues. Promoter methylation was negatively correlated with the local regulation of gene expression. In the distant regulation of gene expression, the methylation of hypermethylated genes was more likely to be negatively correlated with gene expression, while the methylation of hypomethylated genes was more likely to be positively correlated with gene expression. Moreover, we identified four cervical cancer-specific methylation markers, cg07211381 (RAB3C), cg12205729 (GABRA2), cg20708961 (ZNF257), and cg26490054 (SLC5A8), with 96.2% sensitivity and 95.2% specificity by using the tenfold cross-validation of TCGA data. The four markers could distinguish tumors from normal tissues with a 94.2, 100, 100, and 100% AUC in four independent validation sets from the GEO database. Overall, our study demonstrates the potential use of methylation markers in cervical cancer diagnosis and may boost the development of new epigenetic therapies.

scholarly journals Characterization of histone modifications associated with DNA damage repair genes upon exposure to gamma rays in Arabidopsis seedlings

2016 ◽  
Vol 57 (6) ◽  
pp. 646-654 ◽  
Author(s):  
Suvendu Mondal ◽  
Young Sam Go ◽  
Seung Sik Lee ◽  
Byung Yeoup Chung ◽  
Jin-Hong Kim
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Gamma Irradiation ◽  
Histone Modifications ◽  
Gamma Rays ◽  
Regulation Of Gene Expression ◽  
Chromatin Modification ◽  
Histone H3 ◽  
Marker Genes ◽  
Transcription Start Sites

Abstract Dynamic histone modifications play an important role in controlling gene expression in response to various environmental cues. This mechanism of regulation of gene expression is important for sessile organisms, like land plants. We have previously reported consistent upregulation of various marker genes in response to gamma rays at various post-irradiation times. In the present study, we performed various chromatin modification analyses at selected loci using the standard chromatin immunoprecipitation procedure, and demonstrate that upregulation of these genes is associated with histone H3 lysine 4 tri-methylation (H3K4me3) at the gene body or transcription start sites of these loci. Further, at specific AtAgo2 loci, both H3K4me3 and histone H3 lysine 9 acetylation (H3K9ac) are important in controlling gene expression in response to gamma irradiation. There was no change in DNA methylation in these selected loci. We conclude that specific histone modification such as H3K4me3 and H3K9ac may be more important in activating gene expression in these selected loci in response to gamma irradiation than a change in DNA methylation.

P5283The prognostic value of contouring papillary muscles vs. simplified contouring in CMR volumetry of the left ventricle

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Haney ◽  
J Riffel ◽  
H A Katus ◽  
M G Friedrich ◽  
M Ochs
Keyword(s):  
Prognostic Value ◽  
Cox Regression ◽  
Left Ventricular ◽  
Measurement Methods ◽  
Absolute Difference ◽  
Papillary Muscles ◽  
Myocardial Mass ◽  
Significant Difference ◽  
Non Ischemic Dilated Cardiomyopathy ◽  
Exclusion Method

Abstract Background Cardiovascular magnetic resonance (CMR) has evolved as a gold standard for the quantitative assessment of functional parameters. While only inclusion of trabecles and papillary muscles (TPM) accurately reflects anatomy, a simplified approach is frequently used, that “cuts off” this tissue when contouring. Current recommendations favour their inclusion yet also allow for a simplified method. No data exist on any impact of the selection of methods on the prognostic value of the CMR findings. Purpose We aimed to assess the prognostic value of left ventricular (LV) volumetry in non-ischemic dilated cardiomyopathy (NIDCM) assessed by CMR with (1) the exclusion method (accounting TPM to LV cavity volume) or (2) the inclusion method (accounting TPM to LV mass). Furthermore, the predictive value of measuring myocardial mass in end-systole compared with end-diastole was evaluated. Methods Three-hundred forty-six patients with NIDCM who had undergone CMR examination between 2005 and 2013 were enrolled for retrospective analysis. Left ventricular endo- and epicardial contours were acquired by semi-automatic threshold detection in end-diastole and in end-systole, both with the inclusion and the exclusion method. The combined endpoint was cardiac death, heart transplantation, cardiac decompensation, ventricular tachycardia or ventricular fibrillation. Cox regression analysis was performed to evaluate prognostic impact. Results Primary endpoint occurred in 76 patients during a median follow-up of 4.5 years. A significant absolute difference between the two measurement methods was shown for ejection fraction (EF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV) and myocardial mass both in end-systole and end-diastole (p<0.05). Correlation analyses showed significant direct correlation between the two measurement methods. However, in multivariate Cox regression, there was no significant difference in prediction of the combined endpoint between using the inclusion or the exclusion method for EF, LVESV, LVEDV and myocardial mass. Similarly, there was no significant difference in analysis of myocardial mass in end-diastole compared with end-systole. Conclusion In patients with non-ischemic dilated cardiomyopathy, there is no impact of the contouring method (inclusion vs. exclusion of trabecular tissue an papillary muscles from myocardial tissue) on the prognostic value of a CMR volumetry. Although there is a significant absolute difference in measurements, the prediction of adverse events is not influenced.

Risk Factors for Primary Arteriovenous Fistula Dysfunction in Hemodialysis Patients: A Retrospective Survival Analysis in Multiple Medical Centers

2019 ◽  
Vol 48 (3) ◽  
pp. 276-282 ◽  
Author(s):  
Maowan Wen ◽  
Zheng Li ◽  
Jun Li ◽  
Wen Zhou ◽  
Yu Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Flow ◽  
Survival Analysis ◽  
Arteriovenous Fistula ◽  
Cox Regression ◽  
Autoimmune Disorder ◽  
Major Barrier ◽  
Cox Regression Analysis ◽  
Medical Centers ◽  
Significant Difference

Background: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis (HD). However, primary AVF dysfunction represents a major barrier to the long-term success of HD therapy. This study aims to analyze the variables that influence the incidence of first AVF failure in HD patients. Methods: From January 2012 to October 2016, a total of 100 HD subjects from 43 medical centers were enrolled for a retrospective survival analysis of AVF dysfunction. To diminish the potential influence of surgeon experiences, the same operation group in Second Xiangya Hospital performed all studied AVF placements. This study focuses on a Chinese population of idiopathic glomerular disease to avoid the secondary influence of other systemic diseases, including diabetes, hypertension, and autoimmune disorder. AVF dysfunction was defined as lower blood flow during dialysis (≤200 mL/min) or insufficiency of HD treatment caused by reduced blood flow. Results: Among all enrolled subjects, the incidence of AVF dysfunction due to impatency was 27% (n = 27) with a cumulative survival of 84.0, 73.1, and 71.6% in 6, 12, and 24 months of post-placement. AVF survival ­analysis revealed a higher incidence of AVF failure in females (p= 0.025) and elderly (p = 0.031) patients. Importantly, AVF dysfunction markedly increased in subjects with higher levels of platelets (PLTs; p = 0.024), severe anemia (p = 0.014), and extended temporary catheter retention (p = 0.020). Further multivariate Cox regression analysis confirmed these variables as independent risk factors for first AVF dysfunction. Meanwhile, no significant difference could be observed according to the levels of body mass index, serum albumin, serum calcium, serum phosphorus, prothrombin time, and activated partial thromboplastin time. Lastly, anti-coagulant treatments seemed to barely influence the outcomes of AVF survival in this study. Conclusion: These findings suggest that primary AVF dysfunction in HD patients is associated with gender, ageing, PLT counting number, hemoglobin level, and retention time of temporary catheter.

Surprising Lack of Correlation between CD38 and Time to First Treatment in Chronic Lympocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2058-2058
Author(s):  
Matthew S. Kaufman ◽  
Rajendra Damle ◽  
Nina Kohn ◽  
Christina Johnson ◽  
Nancy Driscoll ◽  
...  
Keyword(s):  
Statistical Difference ◽  
Prognostic Markers ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Tertiary Care ◽  
Small Sample ◽  
Mutation Status ◽  
Cd38 Expression ◽  
Significant Difference ◽  
Time To First Treatment

Abstract BACKGROUND: Although IgVH gene mutation status and expression of CD38 are accepted prognostic markers of patient survival in chronic lymphocytic leukemia(CLL), the relative value of these two markers continues to vex even experts in the field. METHODS: To address this issue we evaluated mutation status and CD38 expression in 159 patients and examined time to first treatment(TTT), as a surrogate endpoint for survival, in various combinations of factors. IgVH gene and CD38 analyses were performed according to standard practice. TTT was analyzed using the product limit method and compared using the log rank test. For these analyses, subjects who had not yet started treatment at the time of cut-off (July 2007) or were lost-to-follow-up were considered censored. A Cox proportional hazards model was used to examine the joint effects of CD38 and mutation status on starting treatment. RESULTS: The two tables show TTT for each CD38 and mutation status independently and in combination. Median TTT for CD38- patients(n=88) was 79 months(95% CI: 60–144) vs 60 months(95% CI: 45–153) for CD38+ patients(n=71). This did not represent a statistical difference(p=0.1891). On the other hand, there was a statistical difference in TTT based on mutation(p&lt;0.0001). Median TTT for mutated patients(n=73) was 192 months(95% CI: 96-not estimable(NE)) vs 48 months(95% CI: 45–60) for unmutated patients(n=86). Cox regression showed that unmutated patients were 2.7 times more likely to start treatment than patients who were mutated(p&lt;0.006). There was a significant difference in TTT based on CD38 status and mutation status combined(p&lt;0.0009). Pair-wise comparisons indicate that: TTT was significantly longer for patients who were CD38-/mutated than for patients who were CD38+/unmutated(p=0.0013); TTT was significantly longer for patients who were CD38-/mutated than for patients who were CD38-/unmutated(p=0.0137). Although the median TTT is longer for CD38+/mutated patients(192 mo) than for the CD38-/mutated patients(120 mo), it is not statistically significant(p=0.7725) and may be effected by the relatively small sample size of the former(n=18). CONCLUSIONS: These data confirm the significant prognostic value of mutation status and time to first treatment in CLL. Surprisingly, and in contrast to a recent report(Rassenti et al, Blood, in press), our results with CD38 expression reveal a lesser level of influence. These findings must be cautiously interpreted to avoid potentially confounding factors. First, a selection bias in patients referred to a tertiary care institution in terms of disease severity or aberrant clinical course may exist. Second, TTT decisions are, to some extent, subjective and our threshold for initiating treatment may be higher than of other hematologists-oncologists. Our data confirm that newly identified prognostic markers need further evaluation. Univariate Analysis n Median Time to Treat(95% CI) Total unmutated 86 48 mo (45–60) Total mutated 73 192 mo (96-not estimable) Total CD38+ 71 60 mo (45–153) Total CD38– 88 79 mo (60–144) Multivariate Analysis n Median TTT(95% CI) unmutated CD38+ 54 57 mo (36–72) mutated CD38+ 17 192 mo (72-not estimable) unmutated CD38– 32 48 mo (42–66) mutated CD38– 56 120 mo (79-not estimable)

scholarly journals EGTA, a calcium chelator, affects cell cycle and increases DNA methylation in root tips of Triticum aestivum L.

2016 ◽  
Vol 85 (3) ◽  
Author(s):  
Caiyun Zhang ◽  
Wenshuo Shi ◽  
Keshi Ma ◽  
Hongjie Li ◽  
Feixiong Zhang
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
Triticum Aestivum ◽  
Random Amplified Polymorphic Dna ◽  
Dna Polymorphisms ◽  
Pcr Analysis ◽  
Marker Genes ◽  
Restriction Enzyme Digestion ◽  
Gene Markers ◽  
The Impact

In this study, when germinated <em>Triticum aestivum</em> L. seeds were treated with 0, 2, 4 and 6 mM ethyl glycol tetraacetic acid (EGTA), root growth was suppressed and the mitotic index decreased. These inhibitory effects were positively correlated with EGTA concentration. RT-PCR analysis revealed that the expression of several gene markers related to the G1/S transition of the cell cycle were significantly downregulated. Confocal microscopy of Fluo-3/AM-stained roots showed chelation of nearly all of the Ca<sup>2+</sup> within the root meristematic regions. Both random amplified polymorphic DNA (RAPD) and coupled restriction enzyme digestion-random amplification (CRED-RA) techniques showed significant increases in the levels of genomic DNA polymorphisms and degree of DNA methylation. The study provides information concerning the impact of Ca<sup>2+</sup> chelator, EGTA, on the growth, expression of cell cycle transition marker genes, and changes in DNA structure and methylation in the wheat roots.

scholarly journals A novel epigenetic signature for predicting the prognosis of pancreatic ductal adenocarcinoma

2020 ◽  
Author(s):  
Zhiming Zhao ◽  
Mengyang Li ◽  
Xianglong Tan ◽  
Rong Liu
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Regression Analysis ◽  
Survival Analysis ◽  
Prognostic Factors ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cox Regression ◽  
Risk Groups ◽  
Ductal Adenocarcinoma ◽  
Cox Regression Analysis

Abstract Background Aberrant DNA methylation is often involved in carcinogenesis. This study is designed to establish an epigenetic signature to predict overall survival (OS) of pancreatic ductal adenocarcinoma (PDAC). Methods DNA methylation and RNA-seq data of PDAC patients were downloaded from the Cancer Genome Atlas database, Genotype-Tissue Expression (GTEx), and International Cancer Genome Consortium (ICGC) database. Methylation-related differentially expressed genes (DEGs) were identified using an R package MethylMix. Epigenetic signature and nomogram were established by the LASSO and multivariate Cox regression analysis, respectively. In addition, a joint survival analysis of the gene expression and methylation was performed to identify potential prognostic factors for patients with PDAC. Results There were a total of 56 methylation-related DEGs by MethylMix criteria. After LASSO Cox regression analysis, we developed an epigenetic signature composed of five genes according to their methylation level. The signature was able to divide patients into high-risk and low-risk groups, and the OS between the high-and low-risk groups was more significantly different in both training and validation cohort. The signature is independent of clinicopathological variables and indicated better predictive power. Moreover, we developed a novel prognostic nomogram that combines risk scores with three clinicopathological factors. The joint survival analysis of gene expression and methylation revealed that 24 genes could be independent prognostic factors for OS in PDAC. Conclusions The qualitative signature and nomogram that predict OS at the individualized level and guide therapy for patients with PDAC.

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