Liver Hepatocellular Carcinoma: Correlation between mRNA expression and DNA methylation
(primary solid tumor cohort)
Maintained by Richard Park (Boston University/Harvard Medical School)
Overview
Introduction

The role of general epigenetic mechanisms in carcinogenesis and tumor aggressiveness is well documented: CpG island hyper-methylation silences tumor suppressor genes, whereas hypo-methylation promotes the transcriptional activation of oncogenes and induces chromosomal instability. This pipeline calculates and identifies correlations between DNA methylation and gene expression profiles using the available array technologies.

Summary

The top 25 correlated methylation probes per gene are displayed. Total number of matched samples = 68. Number of gene expression samples = 69. Number of methylation samples = 68.

Results
Correlation Histogram

Figure 1.  Histogram of methylation correlation values. n is the number of matched samples between Level 3 CpG site methylation and Level 3 gene expression arrays. Number of Matched Samples = 68

Qvalue Summary Plots

Figure 2.  Plot 1. The estimated pi_0 versus the tuning parameter lambda. Plot 2. The q-values versus the p-values. Plot 3. The number of significant tests versus each q-value cutoff. Plot 4. The number of expected false positives versus the number of significant tests.The first is a plot of the estimate of pi_0 versus its tuning parameter lambda. In most cases, as lambda gets larger, the bias of the estimate decreases, yet the variance increases. Comparing your estimate of pi_0 to this plot allows one to guage its quality. The remaining three plots show how many tests are significant, as well as how many false positives to expect for each q-value cut-off.

Negative Correlation between Methylation and Gene Expression

Table 1.  Get Full Table Top 25 most negatively correlated methylation probes. Correlation Coefficient: See Methods & Data below. Pval and Qval: P- and Q-values of the correlation coefficient. Expression Mean: mean detection level of gene expression probes. Methylation Mean: mean detection level of CpG methylation probes.

Meth_Probe Gene Chrom Position Corr_Coeff Pval Qval Expr_Mean Meth_Mean
cg21550016 LOC654433 2 113992930 -0.91 0 0 5.656 0.729300
cg06907626 NPC1L1 7 44580809 -0.87 0 0 7.469 0.647082
cg08036899 IFI27 14 94577218 -0.87 0 0 10.853 0.713177
cg24046411 CYBA 16 88717646 -0.86 0 0 9.607 0.571978
cg18338296 THRSP 11 77775044 -0.86 0 0 6.738 0.669650
cg14476101 PHGDH 1 120255992 -0.85 0 0 10.093 0.525119
cg07364841 HGFAC 4 3444147 -0.84 0 0 NA 0.757898
cg13640769 C14orf68 14 100789624 -0.84 0 0 NA 0.693479
cg16408081 PTPRCAP 11 67205869 -0.84 0 0 6.766 0.773841
cg06277277 NR1I3 1 161208307 -0.84 0 0 9.221 0.329895
cg22721334 ZSCAN18 19 58609618 -0.84 0 0 8.279 0.302887
cg16530498 HSD17B14 19 49339776 -0.83 0 0 8.367 0.212577
cg24724633 ZFP82 19 36909413 -0.83 0 0 NA 0.312768
cg19835040 RTP3 3 46538742 -0.83 0 0 NA 0.382653
cg04145765 TRIM55 8 67039461 -0.83 0 0 NA 0.467485
cg08713365 NRSN2 20 327623 -0.83 0 0 7.566 0.552251
cg02349096 RAB3D 19 11450198 -0.83 0 0 7.383 0.371120
cg27436259 PRSS8 16 31147017 -0.83 0 0 NA 0.697003
cg07906527 ETNK2 1 204116483 -0.83 0 0 10.831 0.529732
cg27373972 B3GALT4 6 33244788 -0.82 0 0 5.776 0.484589
cg20451566 GTSF1 12 54867454 -0.82 3.9e-13 1.9e-12 NA 0.639981
cg06251289 CMTM3 16 66639593 -0.82 0 0 8.360 0.527912
cg14825555 SFN 1 27190639 -0.82 0 0 NA 0.504672
cg08862162 TAT 16 71610334 -0.82 0 0 12.218 0.576519
cg03151554 BCL2L10 15 52405123 -0.82 0 0 NA 0.809668
cg07136635 PELO 5 52096641 -0.82 0 0 9.175 0.285034
Methods & Data
Input

Methylation Array Platforms: Illumina Infinium HumanMethylation27, Illumina DNA Methylation OMA002, Illumina DNA Methylation OMA003

  • methylation file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MethylationPreprocess/LIHC-TP/2900810/0.GDAC_MethylationPreprocess.Finished/LIHC-TP.meth.for_correlation.filtered_data.txt

Gene Expression Platforms: Agilent 244K Gene Expression G4502A-07-1, Agilent 244K Gene Expression G4502A-07-2, Agilent 244K Gene Expression G4502A-07-3, Affymetrix Human Exon 1.0 ST Array, Affymetrix HT Human Genome U133 Array

  • gene expression file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/mRNAseq_preprocessor/LIHC-TP/2844036/LIHC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

Correlation Coefficient

Level 3 methylation and gene expression arrays were paired on the basis of Entrez Gene ID concordance. The association between CpG site methylation and the level of expression of the corresponding genes was determined by calculating a correlation measure between the two platforms.

  • correlation measure = Spearman

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.