Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma

Table 6

(a) The pathways analysis for 74 significant proteins in the total stage carcinogenesis. (b) The pathway analysis and gene set enrichment analysis of the 74 proteins of total-stage liver cancer on () biological processes, () cellular components, and () molecular functions by NOA.

(a)

Rank	Term	Count	Symbol	value
KEGG
1	hsa04110:Cell cycle	14	E2F1, CDK1, PRKDC, CDC20, MCM2, MCM3, YWHAE, MCM4, CDK2, MCM7, GSK3B, PCNA, BUB1B, MYC
2	hsa05215:Prostate cancer	7	E2F1, HSP90AB1, GRB2, GSK3B, MAPK3, PTEN, CDK2
3	hsa04114:Oocyte meiosis	7	CDK1, PPP1CA, MAPK3, CDC20, AURKA, YWHAE, CDK2
4	hsa03030:DNA replication	5	MCM7, PCNA, MCM2, MCM3, MCM4
5	hsa05200:Pathways in cancer	10	E2F1, HSP90AB1, TRAF2, GRB2, MSH2, GSK3B, MAPK3, MYC, PTEN, CDK2
6	hsa05213:Endometrial cancer	5	GRB2, GSK3B, MAPK3, MYC, PTEN
7	hsa05210:Colorectal cancer	5	GRB2, MSH2, GSK3B, MAPK3, MYC	0.002457
8	hsa05222:Small cell lung cancer	5	E2F1, TRAF2, MYC, PTEN, CDK2	0.002457
9	hsa05214:Glioma	4	E2F1, GRB2, MAPK3, PTEN	0.008946
10	hsa04722:Neurotrophin signaling pathway	5	GRB2, GSK3B, MAPK3, YWHAE, TP73	0.009832
11	hsa04115:p53 signaling pathway	4	CDK1, PTEN, CDK2, TP73	0.011029
12	hsa05220:Chronic myeloid leukemia	4	E2F1, GRB2, MAPK3, MYC	0.014381
13	hsa04914:Progesterone-mediated oocyte maturation	4	HSP90AB1, CDK1, MAPK3, CDK2	0.020705
14	hsa04012:ErbB signaling pathway	4	GRB2, GSK3B, MAPK3, MYC	0.021345
15	hsa04540:Gap junction	4	CDK1, GRB2, MAPK3, TUBA1B	0.022657
16	hsa05219:Bladder cancer	3	E2F1, MAPK3, MYC	0.033366
17	hsa04510:Focal adhesion	5	PPP1CA, GRB2, GSK3B, MAPK3, PTEN	0.047655
18	hsa05223:Non-small cell lung cancer	3	E2F1, GRB2, MAPK3	0.052694
19	hsa05221:Acute myeloid leukemia	3	GRB2, MAPK3, MYC	0.059845
20	hsa04910:Insulin signaling pathway	4	PPP1CA, GRB2, GSK3B, MAPK3	0.064636
21	hsa05218:Melanoma	3	E2F1, MAPK3, PTEN	0.085159
22	hsa04662:B cell receptor signaling pathway	3	GRB2, GSK3B, MAPK3	0.09351
BioCarte
1a	h_g1Pathway:Cell Cycle:G1/S Check Point	4	E2F1, CDK1, GSK3B, CDK2	0.012616
2a	h_p27Pathway:Regulation of p27 Phosphorylation during Cell Cycle Progression	3	E2F1, NEDD8, CDK2	0.020162
3a	h_p53Pathway:p53 Signaling Pathway	3	E2F1, PCNA, CDK2	0.033691
4a	h_her2Pathway:Role of ERBB2 in Signal Transduction and Oncology	3	GRB2, MAPK3, ESR1	0.049866
5a	h_ptenPathway:PTEN dependent cell cycle arrest and apoptosis	3	GRB2, MAPK3, PTEN	0.054277
6a	h_RacCycDPathway:Influence of Ras and Rho proteins on G1 to S Transition	3	E2F1, MAPK3, CDK2	0.063496
7a	h_cellcyclePathway:Cyclins and Cell Cycle Regulation	3	E2F1, CDK1, CDK2	0.068295

The significant pathways via DAVID Bioinformatics database are selected for the 74 significant proteins in carcinogenesis. Bold indicates value > 0.05. Most of them are from the KEGG database, and we add several key pathways from BioCarta.

(b)

GO:term	value	Corrected value					Term name
() Biological processes
GO:0051320			6357	9	12	4	S phase
GO:0000084			6357	9	12	4	S phase of mitotic cell cycle
GO:0006267			6357	9	16	4	Prereplicative complex assembly
GO:0065004			6357	9	68	5	Protein-DNA complex assembly
GO:0000727			6357	9	26	4	Double-strand break repair via break-induced replication
GO:0006270			6357	9	28	4	DNA-dependent DNA replication initiation
GO:0022616			6357	9	31	4	DNA strand elongation
GO:0006271			6357	9	31	4	DNA strand elongation involved in DNA replication
GO:0000724			6357	9	38	4	Double-strand break repair via homologous recombination
GO:0022402			6357	9	445	7	Cell cycle process
() Cellular components
GO:0042555			6357	9	6	4	MCM complex
GO:0005656			6357	9	16	4	Prereplicative complex
GO:0031261			6357	9	22	4	DNA replication preinitiation complex
GO:0031298			6357	9	25	4	Replication fork protection complex
GO:0032993			6357	9	46	4	Protein-DNA complex
GO:0043234			6357	9	1369	9	Protein complex
GO:0044454			6357	9	217	5	Nuclear chromosome part
GO:0044451			6357	9	275	5	Nucleoplasm part
GO:0044428			6357	9	1251	8	Nuclear part
GO:0044427		0.0011	6357	9	302	5	Chromosomal part
() Molecular functions
GO:0043566			6357	9	85	6	Structure-specific DNA binding
GO:0043138			6357	9	18	4	3′-5′ DNA helicase activity
GO:0004003			6357	9	26	4	ATP-dependent DNA helicase activity
GO:0003682			6357	9	80	5	Chromatin binding
GO:0003688			6357	9	30	4	DNA replication origin binding
GO:0003678			6357	9	39	4	DNA helicase activity
GO:0003697			6357	9	44	4	Single-stranded DNA binding
GO:0016887			6357	9	278	6	ATPase activity
GO:0043140			6357	9	13	3	ATP-dependent 3′-5′ DNA helicase activity
GO:0008094			6357	9	67	4	DNA-dependent ATPase activity

: number of genes in reference set.
: number of genes in test set.
: number of genes annotated by given term in reference set.
: number of genes annotated by given term in test set.