Bioinformatics analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma

doi:10.3748/wjg.v24.i24.2605

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 24, Issue 24

This Article

Academic Content and Language Evaluation of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (10352)

All Articles published online

The chart showing PDF series, HTML series, Figures (1-5) series, Tables (1-5) series.

Item

Count

PDF

703

HTML

5748

Figures (1-5)

326

Tables (1-5)

799

Sum=7576

Publishing Process of This Article

The chart showing Browse series, Download series.

Item

Count

Browse

1267

Download

1509

Sum=2776

Jun 28, 2018 (publication date) through Dec 24, 2024

Times Cited of This Article

Times Cited (50)

Journal Information of This Article

Publication Name

World Journal of Gastroenterology

ISSN

1007-9327

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Gastroenterol. Jun 28, 2018; 24(24): 2605-2616
Published online Jun 28, 2018. doi: 10.3748/wjg.v24.i24.2605

Table 1 GO enrichment analysis of methylated-differentially expressed genes related with hepatocellular carcinoma

Category		Term	Count	%	P value
Hyper-LGs	GOTERM_BP_FAT	GO:0048545~response to steroid hormone stimulus	18	6.79	1.51E-08
	GOTERM_BP_FAT	GO:0009725~response to hormone stimulus	24	9.06	3.15E-08
	GOTERM_BP_FAT	GO:0007166~cell surface receptor linked signal transduction	60	22.64	1.75E-07
	GOTERM_BP_FAT	GO:0009719~response to endogenous stimulus	24	9.06	1.89E-07
	GOTERM_BP_FAT	GO:0007610~behavior	25	9.43	6.76E-07
	GOTERM_CC_FAT	GO:0044421~extracellular region part	48	18.11	1.97E-11
	GOTERM_CC_FAT	GO:0005886~plasma membrane	107	40.38	9.53E-10
	GOTERM_CC_FAT	GO:0005576~extracellular region	68	25.66	1.10E-08
	GOTERM_CC_FAT	GO:0044459~plasma membrane part	71	26.79	3.27E-08
	GOTERM_CC_FAT	GO:0031226~intrinsic to plasma membrane	47	17.74	1.22E-07
	GOTERM_MF_FAT	GO:0005539~glycosaminoglycan binding	11	4.15	7.78E-05
	GOTERM_MF_FAT	GO:0004714~transmembrane receptor protein tyrosine kinase activity	8	3.02	8.88E-05
	GOTERM_MF_FAT	GO:0001871~pattern binding	11	4.15	1.72E-04
	GOTERM_MF_FAT	GO:0030247~polysaccharide binding	11	4.15	1.72E-04
	GOTERM_MF_FAT	GO:0004713~protein tyrosine kinase activity	11	4.15	3.15E-04

Hypo-HGs	GOTERM_BP_FAT	GO:0006260~DNA replication	10	6.25	6.22E-05
	GOTERM_BP_FAT	GO:0051301~cell division	12	7.50	8.37E-05
	GOTERM_BP_FAT	GO:0051276~chromosome organization	15	9.38	1.41E-04
	GOTERM_BP_FAT	GO:0006259~DNA metabolic process	15	9.38	2.19E-04
	GOTERM_BP_FAT	GO:0007049~cell cycle	19	11.88	2.44E-04
	GOTERM_CC_FAT	GO:0005694~chromosome	14	8.75	3.77E-04
	GOTERM_CC_FAT	GO:0044427~chromosomal part	12	7.50	1.01E-03
	GOTERM_CC_FAT	GO:0000793~condensed chromosome	7	4.38	1.34E-03
	GOTERM_CC_FAT	GO:0000785~chromatin	8	5.00	2.77E-03
	GOTERM_CC_FAT	GO:0044421~extracellular region part	19	11.88	3.60E-03
	GOTERM_MF_FAT	GO:0030414~peptidase inhibitor activity	6	3.75	1.24E-02
	GOTERM_MF_FAT	GO:0016849~phosphorus-oxygen lyase activity	3	1.88	1.65E-02
	GOTERM_MF_FAT	GO:0009975~cyclase activity	3	1.88	1.80E-02
	GOTERM_MF_FAT	GO:0004857~enzyme inhibitor activity	7	4.38	3.53E-02
	GOTERM_MF_FAT	GO:0008092~cytoskeletal protein binding	10	6.25	3.83E-02

Top five terms were listed on the basis of P value if over five terms in the category, Hyper-LGs (hypermethylated, lowly expressed genes), Hypo-HGs (hypomethylated, highly expressed genes).

Table 2 KEGG pathway analysis of methylated-differentially expressed genes related with hepatocellular carcinoma

Category		Term	Count	%	P value	Gene
Hyper-LGs	KEGG_PATHWAY	hsa04610:Complement and coagulation cascades	7	2.64	6.62E-03	C7, CR1, CD55, THBD, MASP1, SERPINE1, PLAUR
	KEGG_PATHWAY	hsa05414:Dilated cardiomyopathy	7	2.64	2.50E-02	LAMA2, ITGA9, ADCY1, ADRB1, ITGB8, ADCY5, TGFB3
	KEGG_PATHWAY	hsa05200:Pathways in cancer	15	5.66	2.94E-02	FGFR2, PTGS2, FLT3, PIK3CD, FZD1, TGFB3, MMP2, WNT2, LAMA2, RAC2, NKX3-1, LAMC2, WNT11, HHIP, GSTP1
	KEGG_PATHWAY	hsa04310:Wnt signaling pathway	9	3.40	3.16E-02	WNT2, SFRP5, NKD2, RAC2, PRICKLE1, SFRP1, FZD1, WNT11, FOSL1
	KEGG_PATHWAY	hsa04062:Chemokine signaling pathway	10	3.77	3.97E-02	CXCL1, ADCY1, DOCK2, CCL23, RAC2, TIAM1, ADCY5, PIK3CD, CCL19, CXCL6
Hypo-HGs	KEGG_PATHWAY	hsa04110:Cell cycle	7	4.38	2.32E-03	CCNE2, E2F2, PRKDC, CDC20, MCM2, SFN, PTTG1
	KEGG_PATHWAY	hsa00140:Steroid hormone biosynthesis	3	1.88	9.07E-02	CYP17A1, CYP7A1, UGT2B11

Top five terms were listed on the basis of P value if over five terms in the category, Hyper-LGs (hypermethylated, lowly expressed genes), Hypo-HGs (hypomethylated, highly expressed genes).

Table 3 Hub genes for hypermethylated, lowly expressed genes ranked in cytoHubba

Catelogy	Rank methods in cytoHubba
Catelogy	MNC	Degree	EPC	Closeness	Radiality	Stress
Gene symbol top 10	*PTGS2*	ADCY5	*PTGS2*	*PIK3CD*	*PIK3CD*	*PTGS2*
	*PIK3CD*	*MMP2*	*PIK3CD*	*PTGS2*	*PTGS2*	*PIK3CD*
	ADCY5	*PTGS2*	*MMP2*	*MMP2*	*MMP2*	*MMP2*
	ADCY1	*PIK3CD*	ADCY5	*ESR1*	*ESR1*	PRKG1
	*CXCL1*	PRKG1	ADCY1	PRKG1	TLR2	*ESR1*
	*ESR1*	ADCY1	*ESR1*	TLR2	SERPINE1	FYN
	*MMP2*	*ESR1*	*CXCL1*	FYN	PRKG1	RAC2
	FYN	FYN	TLR2	*CXCL1*	SNAI1	SERPINE1
	TLR2	*CXCL1*	CALCA	SERPINE1	CRP	*CXCL1*
	SERPINE1	TLR2	PTGER2	ADCY5	*CXCL1*	ADCY5

Bold gene symbols were the overlap hub genes in top 10 by six ranked methods respectively in cytoHubba. MNC: Maximum neighborhood component; Degree: Node connect degree; EPC: Edge percolated component.

Table 4 Hub genes for hypomethylated, highly expressed genes ranked in cytoHubba

Catelogy	Rank methods in cytoHubba
Catelogy	MCC	MNC	Degree	EPC	Closeness	Radiality
Gene symbol top 10	*CDC45*	*CDC45*	*CDC45*	*CDC45*	*CDKN3*	*CDKN3*
	*DTL*	*AURKB*	*AURKB*	*AURKB*	*CDC45*	PRKDC
	RACGAP1	*DTL*	*CDKN3*	*CDKN3*	*AURKB*	*CDC45*
	*AURKB*	RACGAP1	*DTL*	*DTL*	PTTG1	PTTG1
	CDC20	CDC20	RACGAP1	RACGAP1	*DTL*	*MCM10*
	*CDKN3*	*CDKN3*	CDC20	CDC20	*MCM2*	BRCA1
	RRM2	*MCM2*	*MCM2*	*MCM2*	*MCM10*	PI3
	*MCM2*	PTTG1	PTTG1	PTTG1	RACGAP1	*AURKB*
	*MCM10*	RRM2	RRM2	RRM2	CDC20	*MCM2*
	MKI67	*MCM10*	*MCM10*	*MCM10*	RRM2	*DTL*

Bold gene symbols were the overlap hub genes in top 10 by six ranked methods respectively in cytoHubba. MCC: Maximal cilque centrality; MNC: Maximum neighborhood component; Degree: Node connect degree; EPC: Edge percolated component.

Table 5 Modules analysis of the protein–protein interaction network

Category	Module	Score	Nodes	Enrichment and pathway description	Genes
Hyper-LGs	1	10.00	10	GO.0005886: plasma membrane	ADRB1, VIPR1, PTGDR, SCTR, CALCA, GPR83, ADCY1, ADCY5, PTGER2, PTGER4
				GO.0007187: G-protein coupled receptor signaling pathway
				GO.0004016: adenylate cyclase activity
				has04080: Neuroactive ligand-receptor interaction
	2	6.00	6	GO.0051953: negative regulation of amine transport	CCL19, ADRA2B, P2RY12, CXCL6, NPY5R, CXCL1
				GO.0008009: chemokine activity
				has04062: Chemokine signaling pathway
	3	5.68	20	GO.0005886: plasma membrane	OXT, SERPINE1, EDNRB, PTGS2, ADRA1A, IL18, CRP, SOCS3, EFNB3, MMP2, EPHB1, TIAM1, EFNA5, TBXA2R, EPHA2, TLR2, SNAI1, FYN, GNA14, PROK2
				GO.0005003: ephrin receptor activity
				GO.0051240: positive regulation of multicellular organismal process
				hsa04360: Axon guidance
	4	4.50	5	GO.0005605: basal lamina	ITGA9, ITGB8, COL6A2, LAMC2, LAMA2
				GO.0030198: extracellular matrix organization
				hsa04512: ECM-receptor interaction
Hypo-HGs	1	17.56	19	GO.0022402: cell cycle process	CDCA5, KIF14, BRCA1, CENPF, RACGAP1, NEK2, CDKN3, DTL, MCM2, MCM10, CDC45, PTTG1, ANLN, CDC20, RRM2, AURKB, MKI67, STIL, CCNE2
				GO.0015630: microtubule cytoskeleton
				GO.0003688: DNA replication origin binding
				hsa04110: Cell cycle
	2	5.00	5	GO.0007188: adenylate cyclase-modulating G-protein coupled receptor signaling pathway	CNR1, CCL20, ADCY6, HTR1D, CCL25
	2	5.00	5	hsa04062: Chemokine signaling pathway	CNR1, CCL20, ADCY6, HTR1D, CCL25
	3	4.50	5	GO.0005615: extracellular space	REN, PLA2G1B, TIMP1, MMP9, VWF

Hyper-LGs: Hypermethylated, lowly expressed genes; Hypo-HGs: Hypomethylated, highly expressed genes.

Citation: Sang L, Wang XM, Xu DY, Zhao WJ. Bioinformatics analysis of aberrantly methylated-differentially expressed genes and pathways in hepatocellular carcinoma. World J Gastroenterol 2018; 24(24): 2605-2616
URL: https://www.wjgnet.com/1007-9327/full/v24/i24/2605.htm
DOI: https://dx.doi.org/10.3748/wjg.v24.i24.2605