DNA Methylome and Transcriptome Maps of Primary Colorectal Cancer and Matched Liver Metastasis

Abstract

Sequencing-based genome-wide DNA methylation, gene expression studies and associated data on paired colorectal cancer (CRC) primary and liver metastasis are very limited. We have profiled the DNA methylome and transcriptome of matched primary CRC and liver metastasis samples from the same patients. Genome-scale methylation and expression levels were examined using Reduced Representation Bisulfite Sequencing (RRBS) and RNA-Seq, respectively. To investigate DNA methylation and expression patterns, we generated a total of 1.01 × 109 RRBS reads and 4.38 x 108 RNA-Seq reads from the matched cancer tissues. Here, we describe in detail the sample features, experimental design, methods and bioinformatic pipeline for these epigenetic data. We demonstrate the quality of both the samples and sequence data obtained from the paired samples. The sequencing data obtained from this study will serve as a valuable resource for studying underlying mechanisms of distant metastasis and the utility of epigenetic profiles in cancer metastasis.

Exploring Potential Epigenetic Biomarkers for Colorectal Cancer Metastasis

“…This approach enabled the simultaneous analysis of DNA methylation patterns and gene expression changes, which provided a multi-dimensional view of the molecular and functional alterations occurring during CRC progression and metastasis to the liver. Using RRBS, a panel of 244 differentially methylated CpGs (DMCs) (68 hypomethylated and 176 hypermethylated) were identified in liver metastatic tissues (n = 10) in comparison to paired (i.e., from the same patients) primary CRC tissues (n = 10) [42,62]. The majority of the 244 DMCs exhibited hypomethylation in the normal colon and primary CRC, which eventually changed to hypermethylation in liver metastasis.…”

“…The majority of the 244 DMCs exhibited hypomethylation in the normal colon and primary CRC, which eventually changed to hypermethylation in liver metastasis. The integration of methylation data (165 DMCs-genes or regulatory regions) with matched transcriptome data showed that the methylation changes of 21 DMCs were highly correlated with alterations in the expression of 20 protein-coding genes linked to those 21 DMCs (a Spearman or Pearson correlation coefficient < 0.4, p-value < 0.05) [42,62]. These 21 DMCs could possibly be epigenetic drivers of CRC metastasis [42].…”

“…The identification of DNA methylation biomarkers involves the use of various methodologies, and their choice depends on whether global or regional methylation analysis is performed [54]. This includes a methylation-specific PCR (MSP), quantitative methylation-specific PCR (Q-MSP), microarray analysis, pyrosequencing, and reduced representation bisulfite sequencing (RRBS) [42,[55][56][57][58][59][60][61][62]. MSP is a PCR-based technique that amplifies specific DNA regions after bisulfite conversion, identifying the methylation status at precise loci using primers targeting methylated or unmethylated sequences [63].…”