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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

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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

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Project description:Purpose:Pulmonary 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 Methods:Sixty-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. Results:At 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). Conclusions:PFT 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.

Project description:The quality of parenting shapes the development of children's emotion regulation. However, the relative importance of parenting in different developmental stages, indicative of sensitive periods, has rarely been studied. Therefore, we formulated four hypothetical developmental timing models to test the stage-specific effects of mothering and fathering in terms of parental autonomy and intimacy in infancy, middle childhood, and late adolescence on adolescents' emotion regulation. The emotion regulation included reappraisal, suppression, and rumination. We hypothesized that both mothering and fathering in each developmental stage contribute unique effects to adolescents' emotion regulation patterns. The participants were 885 families followed from pregnancy to late adolescence. This preregistered study used data at the children's ages of 1 year, 7 to 8 years, and 18 years. At each measurement point, maternal and paternal autonomy and intimacy were assessed with self- and partner reports using the Subjective Family Picture Test. At the age of 18 years, adolescents' reappraisal and suppression were assessed using the Emotion Regulation Questionnaire and rumination using the Cognitive Emotion Regulation Questionnaire. Stage-specific effects were tested comparing structural equation models. Against our hypotheses, the results showed no effects of mothering or fathering in infancy, middle childhood, or late adolescence on adolescents' emotion regulation patterns. The results were consistent irrespective of both the reporter (i.e., self or partner) and the parental dimension (i.e., autonomy or intimacy). In addition to our main results, there were relatively low agreement between the parents in each other's parenting and descriptive discontinuity of parenting across time (i.e., configural measurement invariance). Overall, we found no support for the stage-specific effects of parent-reported parenting in infancy, middle childhood, or late adolescence on adolescents' emotion regulation. Instead, our findings might reflect the high developmental plasticity of emotion regulation from infancy to late adolescence.

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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.

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