Copyright ©The Author(s) 2018.
World J Hepatol. Jan 27, 2018; 10(1): 155-165
Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.155
Table 1 Datasets used for the meta-analysis
NoGEO AccessionPubMed IDHCC samplesAdjacent tissue samples
Table 2 Availability of clinicopathological information on the 11 datasets used for the integrative analysis of genome-wide DNA methylation
Clinical-pathological informationn = 11%
Cirrhosis status in HCC samples655
Child-Pugh/MELD Score327
HCC Etiology1091
Alphafetoprotein level545
Tumor grade545
Tumor stage545
Survival data327
Table 3 Clinicopathological information of the individual datasets and methodology used for methylation analysis
DatasetYearPMIDGEO datasetHCC (n)Controls (n)Liver cirrhosis in HCC samplesEtiology of liver disease (n)Method
12011215001881312Y (12)HBV (3), HCV (4), alcoholic (6)Human methylation 27 DNA analysis bead-chip
22014243066624545Y (120), N (34)HBV (149), HCV (1), nonviral (4)Illumina GoldenGate Methylation Beadarray Cancer Panel I
32014253762922222N/AHBV (1), HCV (9), alcohol (4), other (8)Infinium Humanmethylation 27 Beadchip
4201525945129GSE5926088N/AHBV-HCV-(8)Nimblegen Human DNA Methylation 3 x 720K CpG Island PI
5201121747116GSE297201212N/AN/AAgilent-017075 human hg 18 promoter 800-200
6201020165882GSE180812020Y (20)HCV (20)Illumina Golden Gate Methylation Beadarray Cancer Panel I
7201222234943GSE379886262N/AHBV-HCV-(7), HBV + HCV-(36), HBV-HCV+(6), HBV + HCV+(13)Illumina Human Methylation27 Beadchip
8201324012984GSE44970208N/AHCV (8)Human Methylation27 Beadchip
9201323208076GSE545036666Y (48), N (17), missing (1)HBV-HCV-(19), HCV (19), HBV (13), HBV + HCV (4), missing (11)Infinium Human Methylation 450K Beadchip
10201425093504GSE579565959Y (37), N (21)HBV+(36), HBV-(23)Intinium Ilumanmethylation27 Beadchip
11201425294808GSE607532727Y (26), N (1)HBV (1), HCV (7), alcohol (9), other (10)Iinfinium -450K Human Methy lation Beadchip
Table 4 Top canonical pathways identified by IPA for the genes corresponding to CpG sites in promoter
Ingenuity canonical pathways-log (P-value)Molecules
G-protein coupled receptor signaling3.84E+00DRD5, GNA11, VIPR2, ADCY5, ADRB1, CNR1, PIK3R5, NPY1R, FPR1, FFAR3, NFKBID, MC2R, PDPK1, GRM4, MC3R, CXCR2, PRKAR1B, DRD4, PDE6B, HCAR2, DUSP4, PTGDR
Transcriptional regulatory network in embryonic stem cells3.42E+00MYF5, SIX3, PAX6, GBX2, CDYL, FOXD3, ONECUT1, FOXC1
cAMP-mediated signaling3.22E+00DRD5, VIPR2, ADCY5, ADRB1, CNR1, NPY1R, FPR1, FFAR3, MC2R, GRM4, MC3R, CXCR2, PRKAR1B, DRD4, PDE6B, HCAR2, DUSP4, PTGDR
Table 5 Canonical pathways identified by IPA for the genes with methylation differences in the body of the gene in hepatocellular carcinoma
Ingenuity canonical pathways-log (P-value)Molecules
Aryl hydrocarbon receptor signaling2.48E+00GSTM1, CCND2, TFF1, ALDH1L2, GSTM2, TP73, GSTP1, ALDH3A1
G-protein coupled receptor signaling2.03E+00CAMK2B, RGS7, GABBR1, PDE4D, ADCY2, PDE1C, ADRA1D, NPR3, PDE10A, GRM6, PRKCG
cAMP-mediated signaling1.73E+00CAMK2B, RGS7, GABBR1, PDE4D, ADCY2, PDE1C, NPR3, PDE10A, GRM6