Clinical significance and biological roles of cyclins in gastric cancer

Figures & data

Table 1 The differentially expressed cyclins mRNA in GC

Symbol	Dataset	Sample (tumor/normal)	Fold change	P-value	Gene rank
GC vs normal
CCNA2	Cui et al^Citation41	80/80	2.204	3.02E–05	513
CCNB1	Cui et al^Citation41	80/80	2.006	2.13E–05	484
	Wang et al^Citation42	12/15	2.251	1.20E–02	3,624
CCNB2	Cui et al^Citation41	80/80	3.111	6.38E–04	1,009
	Wang et al^Citation42	12/15	2.555	9.00E–03	3,222
CCND2	Wang et al^Citation42	12/15	2.449	2.27E–04	489
CCNE1	Cui et al^Citation41	80/80	2.232	2.00E–03	1,385
	Wang et al^Citation42	12/15	3.099	7.00E–03	2,918
Gastric intestinal type adenocarcinoma vs normal
CCNA2	D’Errico et al^Citation43	26/31	2.898	1.03E–10	445
CCNB1	D’Errico et al^Citation43	26/31	3.126	1.58E–10	488
CCNB2	D’Errico et al^Citation43	26/31	3.087	2.66E–10	551
CCND2	D’Errico et al^Citation43	26/31	4.016	2.17E–05	3,409
CCNE1	D’Errico et al^Citation43	26/31	3.598	1.71E–08	1,186
	Cho et al^Citation44	20/19	2.059	7.11E–04	1,013
Diffuse gastric adenocarcinoma vs normal
CCNB1	D’Errico et al^Citation43	6/31	2.187	8.00E–03	2,390
CCNE1	Cho et al^Citation44	31/19	2.594	3.35E–06	421
Gastric mixed adenocarcinoma vs normal
CCNA2	D’Errico et al^Citation43	4/31	2.261	6.00E–03	3,126
	Cho et al^Citation44	10/19	2.059	6.20E–04	920
CCNB1	D’Errico et al^Citation43	4/31	3.294	8.00E–03	3,492
	Cho et al^Citation44	10/19	2.406	1.12E–04	414
CCNB2	D’Errico et al^Citation43	4/31	2.168	1.20E–02	4,049
CCND2	D’Errico et al^Citation43	4/31	3.300	8.00E–03	3,462
	Cho et al^Citation44	10/19	2.459	2.00E–03	1,423
CCNE1	D’Errico et al^Citation43	4/31	2.417	1.40E–02	4,360
Gastric adenocarcinoma vs normal
CCNB1	Cho et al^Citation44	4/19	2.516	2.40E–02	1,555

Note: Data were extracted from the Oncomine database.

Abbreviation: GC, gastric cancer.

Figure 1 Cyclins expression in gastric cancer in Oncomine datasets.

Notes: (A) CCNA2, (B) CCNB1, (C) CCNB2, (D) CCND2, and (E) CCNE1. Data were analyzed in Oncomine datasets by comparative meta-analysis.
Abbreviations: GC, gastric cancer; std, standard.

Figure 2 Cyclins expression in GC in TCGA dataset.

Notes: (A) CCNA2, (B) CCNB1, (C) CCNB2, (D) CCND2, and (E) CCNE1. Data were analyzed in TCGA dataset. ***P<0.001.
Abbreviations: GC, gastric cancer; TCGA, The Cancer Genome Atlas.

Figure 3 CCNB1 and CCNE1 expressions in GC Lauren subtype.

Notes: (A) CCNB1 expression in diffuse gastric adenocarcinoma. (B) CCNB1 expression in gastric intestinal type adenocarcinoma. (C) CCNE1 expression in diffuse gastric adenocarcinoma. (D) CCNE1 expression in gastric intestinal type adenocarcinoma. Data were analyzed in TCGA dataset. ***P<0.001.
Abbreviations: GC, gastric cancer; TCGA, The Cancer Genome Atlas.

Figure 4 Prognosis roles of differentially expressed cyclins in GC patients in KM Plotter datasets.

Notes: (A) CCNA2, (B) CCNB1, (C) CCNB2, and (D) CCNE1. Data were analyzed in KM Plotter datasets.
Abbreviations: GC, gastric cancer; KM Plotter, Kaplan–Meier Plotter.

Table 2 The relationship between differentially expressed cyclins and clinicopathological features in previously published studies

	CCNB1	CCNE1
Differentiation	(54)*	NA
Lauren classification	(35)*	(37)*
Tumor size	NA	(37)*
Stage	(54)*	NA
Lymphatic invasion	(54)*	(37)*
Lymph node metastasis	(35, 53, 54)*	NA
Vascular invasion	NS (54)	(37)*
Overall survival	(35)*, NS (53)	NS (37)

Note:

* P<0.05.

Abbreviations: NA, not available; NS, not significant.

Figure 5 Prognosis roles of CCNB1 in different GC patients.

Notes: (A) Prognostic role of CCNE1 in GC patients who received 5-FU-based chemotherapy treatment. (B) Prognostic role of CCNE1 in GC HER2-negative patients. Data were analyzed in KM Plotter datasets.
Abbreviations: GC, gastric cancer; KM Plotter, Kaplan–Meier Plotter.

Table 3 Enrichment analysis of cyclins

	P-value	Z-score	Genes involved
KEGG pathway
Cell cycle	2.252E–08	−1.733198	CCNA2;CCNB2;CCNB1;CCNE1
p53 signaling pathway	1.255E–06	−1.737387	CCNB2;CCNB1;CCNE1
FoxO signaling pathway	0.0008354	−1.724599	CCNB2;CCNB1
Viral carcinogenesis	0.0014146	−1.829714	CCNA2;CCNE1
AMPK signaling pathway	0.0391648	−1.561928	CCNA2
Transcription factors
FOXM1	8.277E–06	−1.918853	CCNA2;CCNB2;CCNB1
SIN3A	0.0069103	−1.730395	CCNA2;CCNB2;CCNB1
NFYA	0.0347278	−1.662154	CCNA2;CCNB2;CCNB1
E2F4	0.0359975	−1.660036	CCNA2;CCNE1

Figure 6 Protein–protein interaction network of differentially expressed cyclins.

Figure S1 The ROC curves of CCNA2, CCNB1, CCNB2, and CCNE1 were constructed for GC diagnosis.

Notes: (A) CCNA2, (B) CCNB1, (C) CCNB2, and (D) CCNE1.
Abbreviations: AUC, area under curve; GC, gastric cancer; ROC, receiver operating characteristic.

Figure S2 The ROC curves of CCNB1 and CCNE1 for GC Lauren subtype classification.

Notes: (A) CCNB1 for diffuse gastric adenocarcinoma. (B) CCNB1 gastric intestinal type adenocarcinoma. (C) CCNE1 for diffuse gastric adenocarcinoma. (D) CCNE1 gastric intestinal type adenocarcinoma.
Abbreviations: AUC, area under curve; GC, gastric cancer; ROC, receiver operating characteristic.

CuiJChenYChouWCAn integrated transcriptomic and computational analysis for biomarker identification in gastric cancerNucleic Acids Res20113941197120720965966

 PubMed Web of Science ®Google Scholar

WangQWenYGLiDPUpregulated INHBA expression is associated with poor survival in gastric cancerMed Oncol2012291778321132402

 PubMed Web of Science ®Google Scholar

D’ErricoMde RinaldisEBlasiMFGenome-wide expression profile of sporadic gastric cancers with microsatellite instabilityEur J Cancer2009453461469

 PubMed Web of Science ®Google Scholar

ChoJYLimJYCheongJHGene expression signature-based prognostic risk score in gastric cancerClin Cancer Res20111771850185721447720

 PubMed Web of Science ®Google Scholar