title: 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.
authors.affiliation: State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Peking Union Medical College &Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Ning
authors.initials: N
authors.lastname: An
authors.affiliation: State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Peking Union Medical College &Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Peking Union Medical College &Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Guiqi
authors.initials: G
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Peking Union Medical College &Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Kaitai
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D056915:DNA Copy Number Variations / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D050437:Genes, Developmental; D052138:Genes, Neoplasm; D023281:Genomics; D006801:Humans; D053208:Kaplan-Meier Estimate; D015201:Meta-Analysis as Topic; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D059467:Transcriptome / Q000235:genetics