Abstract
Cancer is a complex disease where cancer cells express epigenetic and transcriptomic mechanisms to promote tumor initiation, progression, and survival. To extract relevant features from the 2019 Cancer Cell Line Encyclopedia (CCLE), a multi-layer nonnegative matrix factorization approach is used. We used relevant feature genes and DNA promoter regions to construct genomic interaction network to study gene–gene and gene—DNA promoter methylation relationships. Here, we identified a set of gene transcripts and methylated DNA promoter regions for different clusters, including one homogeneous lymphoid neoplasms cluster. In this cluster, we found different methylated transcription factors that affect transcriptional activation of EGFR and downstream interactions. Furthermore, the hippo-signaling pathway might not function properly because of DNA hypermethylation and low gene expression of both LATS2 and YAP1. Finally, we could identify a potential dysregulation of the CD28-CD86-CTLA4 axis. Characterizing the interaction of the epigenome and the transcriptome is vital for our understanding of cancer cell line behavior, not only for deepening insights into cancer-related processes but also for future disease treatment and drug development. Here we have identified potential candidates that characterize cancer cell lines, which give insight into the development and progression of cancers.
Highlights
Cancer is a complex disease where cancer cells express epigenetic and transcriptomic mechanisms to promote tumor initiation, progression, and survival
There are two clusters that are very homogenous and consist of carcinomas and lymphoid neoplasms. These two clusters can be of interest for further investigation, to analyze whether these cancer cell lines consist of a generic DNA promoter methylation and gene expression profile
When we look into the genomic features of a given cluster, a set of transcripts and DNA promoter regions is identified that may explain the separation of the same cancer tissues
Summary
Cancer is a complex disease where cancer cells express epigenetic and transcriptomic mechanisms to promote tumor initiation, progression, and survival. We identified a set of gene transcripts and methylated DNA promoter regions for different clusters, including one homogeneous lymphoid neoplasms cluster. Different hallmarks of cancer have been identified that contribute to the development and propagation of tumors[1] These hallmarks include sustaining proliferative signaling, evading growth suppressors, resisting cell death, and activating invasion and metastasis. Tumor suppressor genes regulate important processes such as preventing unrestrained cellular growth, DNA repair promotion, and cell cycle checkpoint a ctivation[2]. A large number of cancer cells show an increase in methylation of normally unmethylated CpG islands and promoter regions of tumor suppressors and DNA repair g enes[9]. DNA methylation alterations are associated with drug treatment sensitivity, for example, hypermethylation of DAPK in colon and breast cancer[11]. Affect certain pathways that prevent cancer cells from advancing towards apoptosis or other cell death-related mechanisms, as well as towards the development of drug resistance
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