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. 2020 Oct 6;13:9901–9916. doi: 10.2147/OTT.S267812

Table 4.

KEGG Pathway Analysis of Hypermethylated and Hypomethylated Genes

Pathyway Name ID Gene EntrezGene Statistic
A, KEGG pathway analysis of hypermethylated genes
Oxytocin signaling pathway 04921 22 ADCY4,ADCY2,CACNA2D4,MEF2C,PPP1CC,PIK3R2,TRPM2,PPP1R12C,MAP2K2,ADCY8,NRAS,MAPK7,PLCB2,EGFR,ADCY7,KCNJ9,KCNJ6,OXT,CACNG3,CACNG7,CACNG8,FOX C=159
O=22
P=1.19E-03
Estrogen signaling pathway 04915 14 ADCY4,ADCY2,ADCY8,ADCY7,EGFR,AK72,FOS,GPER1,KCNJ6,KCNJ9,NRAS,PIK3R2,PLCB2,MAP2K2 C=100
O=14
P=5.91E-03
Notch signaling pathway 04330 9 RBPJL,CTBP1,DTX1,HES5,JAG2,NOTCH4,NUMBL,NCOR2,MAML1 C=48
O=9
P=9.04E-03
Signaling pathways regulating pluripotency of stem cells 04550 17 DLX5,APC2,AKT2,FGFR3,JAK2,JAK3,ZFHX3,NRAS,MAPK11,REST,MAP2K2,FIK3R2,BMPR11A,WNT10A,FZD1,WNT5B,HAND1 C=142
O=17
P=1.26E-02
Endometrial cancer 05213 8 CTNNA1,APC2,EGFR,AKT2,NRAS,FIK3R2,MAP2K2,CDH1 C=52
O=8
P=1.39E-02
Rap1 signaling pathway 04015 22 ADCY4,EPHA2,RASGRP2,EFNA5,RAPGEF3,ADCY8,RGS14,EGFR,ADCY2,ADCY7,AKT2,FGFR3,PFN3,NRNAS,RALGDS,FIK3R2,RALB,RALA,MAP2K2,MAPK11,PLCB2,CDH1 C=211
O=22
P=1.41E-02
Prolactin signaling pathway 04917 10 AKT2,FOS,JAK3,NRAS,FIK3R2,MAPK11,MAP2K2,TNFRSF11A,SOCS6,SOCS3 C=72
O=10
P=1.52E-02
Adrenergic signaling in cardiomyocytes 04261 17 ADCY7,ADCY4,CACNG3,RAPGEF3,ADCY2,ADCY8,ADRA1A,AKT2,ATP2B1,PPP1CC,MAPK11,CACNG8,PIK3R2,PLCB2,CACNG7,TPM1,CACNA2D4 C=149
O=1 7
1.88E-02
Progesterone-mediated oocyte maturation 04914 11 ADCY4,ADCY2,ADCY8,ADCY7,AKT2,RPS6KA6,MAPK11,FIK3R2,RPS6KA2,MAPD1L1,CCNA1 C=86
O=11
P=2.06E-02
Inflammatory mediator regulation of TRP channels 04750 11 ADCY2,ADCY8,ADCY7,ALOX12,ADCY4,PRKCH,PPP1CC,MAPK11,FIK3R2,PLCB2,PRKCE C=99
O=11
P=2.45E-02
Cholinergic synapse 04725 13 ADCY4,CHAT,ADCY2,ADCY8,ADCY7,AKT2,FOS,KCNJ6,JAK3,NRAS,FIK3R2,PLCB2,SLC18A3 C=113
O=13
P=2.98E-02
Adherens junction 04520 9 SORBS1,BAIAP2,EGFR,CTNNA1,LMO7,PTPRM,ACP1,ACTN4,CDH1 C=73
O=9
P=3.61E-02
SNARE interactions in vesicular transport 04130 4 GOSR2,STX2,VAMP2,STX5 C=34
O=4
P=3.83E-02
Transcriptional misregulation in cancer 05202 18 FLI1,HOXA11,HOXA9,HOXA10,MLLT1,H3F3C,MEF2C,PAX7,PAX5,SPINT1,RXRA,HIST2H3D,PAX8,ZBTB16,WT1,ZBTB17,HIST1H3D,CCNA1 C=179
O=18
P=4.59E-02
Long-term potentiation 04720 9 RAPGEF3,ADCY8,RPS6KA6,GRIN2D,NRAS,PPP1CC,PLCB2,MAP2K2,RPS6KA2 C=67
O=9
P=4.97E-02
C, the number of reference genes in the category; O is the number of genes in the gene set and also in the category, p-value from hypergeometric test
B, KEGG pathway analysis of hypomethylated genes
Endometrial cancer 05213 9 EGFR,CTNNA2,FOXO3,AKT1,CCND1,PIK3CD,MAP2K2,TCF7 C=52
O=9
P=8.51E-04
Nicotine addiction 05033 10 GRIN3B,GRIN3A,GRIN2A,GRIN2D,GRIN2C,GRIN1,GABRD,GABRA5,GABRB3,CACNA1A C=40
O=10
P=1.35E-03
Glioma 05214 10 CDKN2A,EGFR,AKT1,CALML5,PDGFA,MAP2K2,SHC3,CCND1,PIK3CD,CAMK2B C=65
O=10
P=4.33E-03
Acute myeloid leukemia 05221 8 CEBPA,AKT1,MAP2K2,CCND1,PIK3CD,TCF7,RUNX1,CCNA1 C=57
O=8
P=4.62E-03
Signaling pathways regulating pluripotency of stem cells 04550 17 DUSP9,AKT1,NEUROG1,ISL1,ID4,OTX1,MAPK11,MAP2K2,PIK3CD,LHX5,ZIC3,FZD3,WNT5A,WNT7B,AXIN2,WNT5B,WNT10A C=142
O=17
P=4.96E-03
Proteoglycans in cancer 05205 23 FLNC,AKT1,CTTN,ANK1,GPC1,EGFR,IGF2,HOXD10,MAPK11,MAP2K2,PIK3CD,PLCE1,CCND1,TGFB1,FZD3,WNT5A,ACTG1,WNT7B,KDR,CAMK2B,WNT5B,WNT10A,HPSE2 C=204
O=23
P=5.04E-03
Amphetamine addiction 05031 12 GRIN3B,GRIN3A,GRIN2A,GRIN2D,ARC,GRIN2C,GNAS,GRIN1,CALML5,PPP3CC,CAMK2B,CREB5 C=68
O=12
P=5.93E-03
Calcium signaling pathway 04020 21 ADORA2A,ADORA2B,CRIN2A,CRIN2D,GNAS,GNAL,GRIN2C,GRIN1,GRM5,HTR5A,NTSR1,PPP3CC,PLCE1,CALML5,P2RX1,RYR1,CACNA1A,CAMK2B,EGFR,CACNA1H,ORAI3 C=180
O=21
P=7.79E-03
Melanoma 05218 7 CNKN2A,EGFR,AKT1,PDGFA,MAP2K2,CCND1,PIK3CD C=71
O=7
P=7.96E-03
Chronic myeloid leukemia 05220 10 CTBP1,CNKN2A,CTBP2,SHC3,AKT1,MAP2K2,CCND1,PIK3CD,CAMK2B,TGFB1 C=73
O=10
P=9.59E-03
Rap1 signaling pathway 04015 20 ADORA2A,EGFR,EFNA2,ADORA2B,GRIN2A,GNAS,AKT1,GRIN1,KDR,INSR,NGF,MAPK11,MAP2K2,PIK3CD,PLCE1,CALML5,PRKCI,PDGFA,ACTG1,LPAR2 C=211
O=20
P=1.29E-02
Long-term potentiation 04720 10 GRIN2A,GRIN2D,GRIN2C,GRIN1,GRM5,CALML5,PPP3CC,MAP2K2,RPS6KA2,CAMK2B C=67
O=10
P=1.29E-02
Neuroactive ligand-receptor interaction 04080 29 GRIN3B,DRD4,CHRNE,ADORA2A,HEH3,GPR156,ADRA2A,ADORA2B,GRIN3A,GRM5,GRIN1,GABRD,GABRB3,GRIN2C,P2RY8,GRM6,NPBWR1,GRIN2D,GRIN2A,GABRA5,GRIK4,HTR5A,OPRL1,NTSR1,P2RY11,PRSS3,P2RX1,S1PR4,LPAR2 C=275
O=29
P=1.84E-02
Non-small cell lung cancer 05223 7 EGFR,CNKN2A,FOXO3,AKT1,MAP2K2,CCND1,PIK3CD C=56
O=7
P=2.59E-02
Wnt signaling pathway 04310 16 CSNK1A1,CTBP2,WIF1,CTBP1,NFATC1,LRP6,CCND1,PPP3CC,TCF7,FZD3,WNT5A,WNT7B,WNT5B,WNT10A,CAMK2B,AXIN2 C=140
O=16
P=2.97E-02
Pathways in cancer 05200 26 CEBPA,CNKN2A,CTNNA2,EGFR,CTBP2,DAPK3,CTBP1,EPAS1,AKT1,GSTP1,MAH2,PIK3CD,MAP2K2,CCND1,PDGFA,TGFB1,TCF7,WNT5A,TRAF3,FZD3,WNT7B,CAMK2B,WNT5B,AXIN2,CCNA1,WNT10A C=327
O=26
P=3.44E-02
Hippo signaling pathway 04390 17 WTIP,GDF7,DLG1,CTNNA2,AMH,SCRIB,CCND1,TCF7,WNT5A,TGFB1,FZD3,WNT7B,ACTG1,AXIN2,WNT10A,WNT5B,PRKCI C=154
O=17
P=3.47E-02
MAPK signaling pathway 04010 22 DUSP5,EGFR,DUSP9,DUSP8,AKT1,MAPK8IP3,FLNC,ARRB1,MAPT,NFATC3,MEF2C,NGF,MAPK11,PPP3CC,MAP2K2,ARRB2,PDGFA,RPS6KA2,TGFB1,CACNA1A,CACNB1,CACNA1H C=257
O=22
P=3.53E-02
Cocaine addiction 05030 8 GRIN3B,GRIN3A,GRIN1,GNAS,GRIN2C,GRIN2D,GRIN2A,CREB5 C=50
O=8
P=3.54E-02
cAMP signaling pathway 04024 20 GRIN3B,HCN4,ADORA2A,GRIN3A,GRIN1,AKT1,GRIN2C,AMH,GNAS,GRIN2D,GRIN2A,NFATC3,MAP2K2,PIK3CD,PLCE1,CALML5,PDE4D,ACOX3,CAMK2B,CREB5 C=200
O=20
P=3.64E-02
Amyotrophic lateral sclerosis (ALS) 05014 7 GRIN2D,GRIN2C,GRIN1,GRIN2A,MAPK11,PRPH,PPP3CC C=51
O=7
P=3.86E-02
Prolactin signaling pathway 04917 8 CISH,FOXO3,AKT1,MAPK11,MAP2K2,SHC3,CCND1,PIK3CD C=72
O=8
P=4.25E-02
Colorectal cancer 05210 7 AKT1,MSH2,CCND1,PIK3CD,TGFB1,AXIN2,TCF7 C=62
O=7
P=4.27E-02
Oxytocin signaling pathway 04921 15 EEF2,EGFR,GNAS,MEF2C,NFATC3,PIK3CD,CCND1,MAP2K2,PPP3CC,CALML5,OXT,RYR1,ACTG1,CACNB1,CAMK2B C=159
O=15
P=4.41E-02
Glutamatergic synapse 04724 14 GRIN3B,GRIN3A,GRM6,GRM5,GRIN1,SHANK2,GNAS,GRIN2C,GRIN2D,GRIN2A,GRIK4,PPP3CC,CACNA1A,SHANK3 C=116
O=14
P=4.72E-02
Axon guidance 04360 14 SEMA4D,DPYSL2,SEMA6B,EFNA1,EPHA7,LRRC4C,PPP3CC,PLXNA3,SEMA5B,PLXNB3,SLIT1,CXCL12,SEMA3B,NTNG2 C=127
O=14
P=4.73E-02

Abbreviations: C, the number of reference genes in the category; O is the number of genes in the gene set and also in the category, p-value from hypergeometric test.