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

Table 8

(a) The pathways analysis for 80 late stage significant proteins in 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	16	E2F1, CDK1, YWHAZ, YWHAB, CDC20, SFN, MCM2, MCM3, CDK4, MCM4, CDK2, MCM7, PCNA, YWHAQ, BUB1B, CCNA2
2	hsa04114:Oocyte meiosis	8	CDK1, YWHAZ, YWHAB, YWHAQ, CDC20, AURKA, PPP1CC, CDK2
3	hsa03030:DNA replication	5	MCM7, PCNA, MCM2, MCM3, MCM4
4	hsa04115:p53 signaling pathway	4	CDK1, SFN, CDK4, CDK2	0.020496
5	hsa03040:Spliceosome	5	SNRPB, THOC4, LSM2, SF3A2, SF3B4	0.022722
6	hsa05222:Small cell lung cancer	4	E2F1, TRAF2, CDK4, CDK2	0.035432
7	hsa04914:Progesterone-mediated oocyte maturation	4	HSP90AB1, CDK1, CCNA2, CDK2	0.037607
8	hsa00310:Lysine degradation	3	SETDB1, WHSC1, EHMT2	0.055046
9	hsa05200:Pathways in cancer	7	E2F1, HSP90AB1, TRAF2, MSH2, BIRC5, CDK4, CDK2	0.061178
BioCarte
1a	h_p53Pathway:p53 Signaling Pathway	4	E2F1, PCNA, CDK4, CDK2	0.003378
2a	h_cellcyclePathway:Cyclins and Cell Cycle Regulation	4	E2F1, CDK1, CDK4, CDK2	0.010334
3a	h_g1Pathway:Cell Cycle:G1/S Check Point	4	E2F1, CDK1, CDK4, CDK2	0.015615
4a	h_rbPathway:RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage	3	CDK1, CDK4, CDK2	0.019987
5a	h_ranMSpathway:Role of Ran in mitotic spindle regulation	3	RAN, AURKA, KPNA2	0.019987
6a	h_g2Pathway:Cell Cycle:G2/M Checkpoint	3	CDK1, YWHAQ, BRCA1	0.067509
7a	h_RacCycDPathway:Influence of Ras and Rho proteins on G1 to S Transition	3	E2F1, CDK4, CDK2	0.072809

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	10	12	4	S phase
GO:0000084			6357	10	12	4	S phase of mitotic cell cycle
GO:0006267			6357	10	16	4	Prereplicative complex assembly
GO:0000727			6357	10	26	4	Double-strand break repair via break-induced replication
GO:0006270			6357	10	28	4	DNA-dependent DNA replication initiation
GO:0022616			6357	10	31	4	DNA strand elongation
GO:0006271			6357	10	31	4	DNA strand elongation involved in DNA replication
GO:0000724			6357	10	38	4	Double-strand break repair via homologous recombination
GO:0006260			6357	10	120	5	DNA replication
GO:0000725			6357	10	47	4	Recombinational repair
() Cellular components
GO:0042555			6357	10	6	4	MCM complex
GO:0005656			6357	10	16	4	Prereplicative complex
GO:0031261			6357	10	22	4	DNA replication preinitiation complex
GO:0031298			6357	10	25	4	Replication fork protection complex
GO:0032993			6357	10	46	4	Protein-DNA complex
GO:0044454		0.0113	6357	10	217	4	Nuclear chromosome part
GO:0044451		0.0280	6357	10	275	4	Nucleoplasm part
GO:0044428		0.0370	6357	10	1251	7	Nuclear part
GO:0044427		0.0400	6357	10	302	4	Chromosomal part
GO:0043234		0.0656	6357	10	1369	7	Protein complex
() Molecular functions
GO:0043138			6357	10	18	4	3′-5′ DNA helicase activity
GO:0004003			6357	10	26	4	ATP-dependent DNA helicase activity
GO:0003688			6357	10	30	4	DNA replication origin binding
GO:0043566			6357	10	85	5	Structure-specific DNA binding
GO:0003678			6357	10	39	4	DNA helicase activity
GO:0003697			6357	10	44	4	Single-stranded DNA binding
GO:0043140			6357	10	13	3	ATP-dependent 3′-5′ DNA helicase activity
GO:0008094			6357	10	67	4	DNA-dependent ATPase activity
GO:0003682			6357	10	80	4	Chromatin binding
GO:0070035			6357	10	86	4	Purine NTP-dependent helicase 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.