CpG Site-Based Signature Predicts Survival of Colorectal Cancer

Abstract

Background: A critical unmet medical need in clinical management of colorectal cancer (CRC) pivots around lack of noninvasive and or minimally invasive techniques for early diagnosis and prognostic prediction of clinical outcomes. Because DNA methylation can capture the regulatory landscape of tumors and can be measured in body fluids, it provides unparalleled opportunities for the discovery of early diagnostic and prognostics markers predictive of clinical outcomes. Here we investigated use of DNA methylation for the discovery of potential clinically actionable diagnostic and prognostic markers for predicting survival in CRC. Methods: We analyzed DNA methylation patterns between tumor and control samples to discover signatures of CpG sites and genes associated with CRC and predictive of survival. We conducted functional analysis to identify molecular networks and signaling pathways driving clinical outcomes. Results: We discovered a signature of aberrantly methylated genes associated with CRC and a signature of thirteen (13) CpG sites predictive of survival. We discovered molecular networks and signaling pathways enriched for CpG sites likely to drive clinical outcomes. Conclusions: The investigation revealed that CpG sites can predict survival in CRC and that DNA methylation can capture the regulatory state of tumors through aberrantly methylated molecular networks and signaling pathways.

Early results of the integrative epigenomic-transcriptomic landscape of colorectal adenoma and cancer

“…Seven meDEGs were identified as follows: NECAB1 , PCSK2 , AGTR1 , NLGN1 , LRAT , RXRG , and TMEFF2 . Among these genes, the methylation of PCSK2 [ 31 ], AGTR1 [ 32 ], LRAT [ 33 ], RXRG [ 34 ], and TMEFF2 [ 35 ] has been previously reported in CRC. NECAB1 encodes a neuronal calcium-binding protein[ 36 ], and its methylation has been observed in acute myeloid leukemia[ 37 ].…”

Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells

“…In human tissues, DNA methylation showcases the dynamic nature of promoter regulation [40]. In the context of cancer, changes in DNA methylation at promoter sites can lead to a diversity of gene isoforms and even serve as potential disease markers [41][42][43][44], with differences in the chromatin structure at alternative promoters likely responsible for the dysregulation observed in cancers [45]. Often, one promoter is rich in CpG sites, while another is not.…”