Identification of key pathways and genes influencing prognosis in bladder urothelial carcinoma

Figures & data

Figure 1 Volcano plot of the differentially expressed genes.

Notes: Red: upregulation; green: downregulation; black: non-differentially expressed genes.
Abbreviation: P-adj, adjusted P-value.

Figure 2 GSEA results of tumor and adjacent normal tissue samples.

Note: GSEA result of bladder urothelial carcinoma tumor tissue using c2 (A, B) and c5 (C–H) reference gene sets.
Abbreviations: ES, enrichment score; FDR, false discovery rate; GSEA, gene set enrichment analysis.

Figure 3 Heat map of the 256 prognosis-related differentially expressed genes.

Notes: Red: upregulation; green: downregulation.

Table 1 GO term analysis of potential prognosis-DEGs associated with BUC prognosis

Category	GO ID	Term	Count	%	P-value
GOTERM_BP_DIRECT	GO:0007155	Cell adhesion	22	5.64	9.15E-07
GOTERM_BP_DIRECT	GO:0001525	Angiogenesis	12	3.07	2.16E-04
GOTERM_BP_DIRECT	GO:0030818	Negative regulation of cAMP biosynthetic process	4	1.02	0.00114
GOTERM_BP_DIRECT	GO:0001933	Negative regulation of protein phosphorylation	6	1.54	0.001286
GOTERM_BP_DIRECT	GO:0060548	Negative regulation of cell death	5	1.28	0.006908
GOTERM_BP_DIRECT	GO:0045766	Positive regulation of angiogenesis	7	1.79	0.004536
GOTERM_MF_DIRECT	GO:0008201	Heparin binding	18	4.61	3.44E-11
GOTERM_MF_DIRECT	GO:0005509	Calcium ion binding	24	6.15	5.92E-05
GOTERM_MF_DIRECT	GO:0004114	3′,5′-Cyclic nucleotide phosphodiesterase activity	5	1.28	1.66E-04
GOTERM_MF_DIRECT	GO:0005516	Calmodulin binding	10	2.56	8.05E-04
GOTERM_MF_DIRECT	GO:0030553	cGMP binding	4	1.02	0.001269
GOTERM_CC_DIRECT	GO:0031012	Extracellular matrix	23	5.89	7.06E-11
GOTERM_CC_DIRECT	GO:0005886	Plasma membrane	89	22.80	2.59E-07
GOTERM_CC_DIRECT	GO:0005925	Focal adhesion	19	4.87	4.79E-06
GOTERM_CC_DIRECT	GO:0009986	Cell surface	22	5.64	1.57E-05
GOTERM_CC_DIRECT	GO:0005576	Extracellular region	40	10.25	1.19E-04

Abbreviations: GO, gene ontology; DEGs, differentially expressed genes; BUC, bladder urothelial carcinoma; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate.

Table 2 KEGG analysis of potential prognosis-DEGs associated with BUC prognosis

Pathway ID	Name	Count	%	P-value	Genes
hsa04022	cGMP-PKG signaling pathway	14	3.59	3.09E-07	KCNMA1, ADCY5, MRVI1, PRKG1, EDNRA, ADRB3, AGTR1, ATP2B4, PDE2A, RGS2, PLN, PDE5A, MYLK, ADRA1D
hsa04020	Calcium signaling pathway	13	3.33	4.74E-06	PTGER3, PTGFR, EDNRA, AGTR1, ADRB3, ATP2B4, CHRM2, PDE1C, PLN, PDE1A, CAMK2A, MYLK, ADRA1D
hsa04024	cAMP signaling pathway	10	2.56	0.001408	EDNRA, PTGER3, ATP2B4, RAC3, CHRM2, ADCY5, JUN, PLN, PDE4B, CAMK2A
hsa05200	Pathways in cancer	13	3.33	0.006683	LAMA2, EDNRA, AGTR1, FGFR1, VEGFD, FGF7, PTGER3, RAC3, JUN, ADCY5, RUNX1T1, FGF10, FGF2
hsa04010	MAPK signaling pathway	10	2.56	0.007592	FGFR1, CACNA2D1, DUSP2, FGF7, RAC3, JUN, FGF10, FLNC, FGF2, FLNA
hsa04514	Cell adhesion molecules	7	1.79	0.012562	NCAM1, CD34, CNTN1, NRXN1, JAM2, NEGR1, JAM3
hsa05205	Proteoglycans in cancer	8	2.05	0.018787	FGFR1, HSPG2, DCN, THBS1, FLNC, CAMK2A, FGF2, FLNA
hsa04015	Rap1 signaling pathway	8	2.05	0.023834	FGFR1, VEGFD, FGF7, RAC3, ADCY5, FGF10, THBS1, FGF2
hsa04151	PI3K-AKT signaling pathway	10	2.56	0.044252	LAMA2, FGFR1, VEGFD, FGF7, CHRM2, ITGA7, FGF10, THBS1, FGF2, GHR

Abbreviations: KEGG, Kyoto Encyclopedia of Genes and Genomes; DEGs, differentially expressed genes; BUC, bladder urothelial carcinoma; cGMP, cyclic guanosine monophosphate; PKG, protein kinase G; cAMP, cyclic adenosine monophosphate; MAPK, mitogen-activated protein kinases; Rap1, Ras-associated protein 1; PI3K-AKT, phosphoinositide-3-kinase-AKT.

Figure 4 GeneMANIA interaction networks.

Abbreviation: GeneMANIA, gene multiple association network integration algorithm.

Figure 5 Protein–protein interaction networks.

Notes: Black text: prognosis-related differentially expressed genes; Red text: nine hub genes of the prognosis-related differentially expressed genes in the protein–protein interaction networks.

Figure 6 Top three modules from the GeneMANIA interaction networks.

Notes: A: Module 1; B: the enriched GO term and pathways of module 1; C: module 2; D: the enriched GO term and pathways of module 2; E: module 3; F: the enriched GO term and pathways of module 3.

Abbreviations: GeneMANIA, gene multiple association network integration algorithm; GO, gene ontology; cGMP-PKG, cyclic guanosine monophosphate-protein kinase G.

Figure 7 Top 3 modules from the PPI interaction networks.

Notes: A: module 1; B: the enriched GO term and pathways of module 1; C: module 2; D: the enriched GO term and pathways of module 2; E: module 3; F: the enriched GO term and pathways of module 3.

Abbreviations: PPI, protein–protein interaction; GO, gene ontology; cGMP-PKG, cyclic guanosine monophosphate-protein kinase G.

Figure 8 Kaplan–Meier survival curves for BUC patients.

Note: OS stratified by tumor stage.
Abbreviations: BUC, bladder urothelial carcinoma; OS, overall survival.