Dataset Information

Developmental genes significantly afflicted by aberrant promoter methylation and somatic mutation predict overall survival of late-stage colorectal cancer.

ABSTRACT: Carcinogenesis is an exceedingly complicated process, which involves multi-level dysregulations, including genomics (majorly caused by somatic mutation and copy number variation), DNA methylomics, and transcriptomics. Therefore, only looking into one molecular level of cancer is not sufficient to uncover the intricate underlying mechanisms. With the abundant resources of public available data in the Cancer Genome Atlas (TCGA) database, an integrative strategy was conducted to systematically analyze the aberrant patterns of colorectal cancer on the basis of DNA copy number, promoter methylation, somatic mutation and gene expression. In this study, paired samples in each genomic level were retrieved to identify differentially expressed genes with corresponding genetic or epigenetic dysregulations. Notably, the result of gene ontology enrichment analysis indicated that the differentially expressed genes with corresponding aberrant promoter methylation or somatic mutation were both functionally concentrated upon developmental process, suggesting the intimate association between development and carcinogenesis. Thus, by means of random walk with restart, 37 significant development-related genes were retrieved from a priori-knowledge based biological network. In five independent microarray datasets, Kaplan-Meier survival and Cox regression analyses both confirmed that the expression of these genes was significantly associated with overall survival of Stage III/IV colorectal cancer patients.

SUBMITTER: An N

PROVIDER: S-EPMC4686889 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Developmental genes significantly afflicted by aberrant promoter methylation and somatic mutation predict overall survival of late-stage colorectal cancer.

An Ning N Yang Xue X Cheng Shujun S Wang Guiqi G Zhang Kaitai K

Scientific reports 20151222

Carcinogenesis is an exceedingly complicated process, which involves multi-level dysregulations, including genomics (majorly caused by somatic mutation and copy number variation), DNA methylomics, and transcriptomics. Therefore, only looking into one molecular level of cancer is not sufficient to uncover the intricate underlying mechanisms. With the abundant resources of public available data in the Cancer Genome Atlas (TCGA) database, an integrative strategy was conducted to systematically anal ...[more]

PMID: 26691761

Similar Datasets

Project description:PurposePulmonary dysfunction is a prevalent and potentially debilitating late effect of pediatric cancer treatment. We postulated that age, as a surrogate for respiratory developmental status, might be associated with vulnerability to pulmonary injury.Materials and methodsSixty-one children treated with lung radiation at our institution who had undergone a pulmonary function test (PFT) between 1995 and 2016 were analyzed. Data collection included age at diagnosis and treatment, radiation dose and location, spirometry, and plethysmography results. PFTs were normalized according to age, sex, height, and ethnicity, and transformed into standardized z-scores. Obstructive disease was defined as forced expiratory volume in 1 second z score/forced vital capacity z score < -1.645, restrictive as total lung capacity z score < -1.645, and abnormal diffusion as diffusing capacity of the lung for carbon monoxide z score < -1.645. We determined the incidence of PFT abnormalities in our population and estimated the relative risk of developing pulmonary abnormalities using models adjusted for age.ResultsAt a mean age of 24 years (range, 12-31) and time from radiation of 9 years (range, 1-20), the cumulative incidence of any pulmonary abnormality was 34.4%. Among patients with an abnormal PFT, diffusing and restrictive abnormalities were most common (57.1% and 52.4%). When stratified by age at radiation treatment, 66.7% of patients <5 years had a PFT abnormality, compared with 47.6% for aged 5 to 13 and 20.6% for patients >13. Compared with patients >13 years, those <5 years and 5 to 13 years at radiation treatment had a significantly increased risk of an abnormal PFT with an odds ratio of 7.71 (95% confidence interval, 1.17, 51.06) and 3.51 (95% confidence interval, 1.06, 11.57), respectively (P <. 035). Furthermore, this association remained when examining each type of abnormality (P > .05).ConclusionsPFT abnormalities were common among our cohort of childhood cancer survivors treated with lung radiation. Younger age at treatment is associated with an increased risk of developing pulmonary dysfunction, presumably owing to developmental immaturity.

Dataset Information

Developmental genes significantly afflicted by aberrant promoter methylation and somatic mutation predict overall survival of late-stage colorectal cancer.

Publications

Developmental genes significantly afflicted by aberrant promoter methylation and somatic mutation predict overall survival of late-stage colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets