Identification of EZH2-related key pathways and genes in colorectal cancer using bioinformatics analysis.

doi:10.3877/cma.j.issn.2095-3224.2016.06.004

Abstract

Abstract:

Objective

The aim of this study was to investigate the prognosis value of the EZH2 expression and signatures during CRC and uncover their potential mechanisms in colorectal cancer.

Methods

The gene expression profiles of GSE17538 were downloaded from GEO database. The GSE17 538 data-set contained 232 samples. The data was combined by the R2 platform to search the genes which are associated with a significant expression with EZH2. The gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed by R2 platform. The surival curves were estimated using the Kaplan-Meier method.

Results

In 232 cases, the expression of EZH2 in colorectal carcinoma was associated with age (χ²=4.426, P=0.035), AJCC stage (χ²=8.259, P=0.041) and differentiation (χ²=7.301, P=0.026), except for sex(χ²=0.622, P=0.430); In total, 4305 genes were identified which are associated with a significant expression with EZH2, including 2240 up-regulated genes and 2065 down-regulated genes. GO analysis and KEGG pathway analysis results showed that these were significantly enriched in biological processes , including proliferation in cell cycle, RNA transcription and DNA replication; Using the Kaplan-Meier method we found the expression of EZH2 is related with disease free survival .

Conclusion

EZH2 could be used as a potential prognostic marker and a therapeutic target in colorectal cancer.

Key words: Colorectal neoplasms, Gene expression, EZH2, Cell cycle, Gene microarray

Dawei Song, Rui Huang, Qingchao Tang, Tianyi Ma, Yuchen Luo, Guiyu Wang, Xishan Wang. Identification of EZH2-related key pathways and genes in colorectal cancer using bioinformatics analysis.[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2016, 05(06): 475-479.

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Figures/Tables 5

References 16

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基因	相关系数	P值	基因	相关系数	P值
NCAPG2	0.73	<0.001	PXDC1	-0.535	<0.001
FANCI	0.724	<0.001	YPEL5	-0.51	<0.001
DBF4	0.717	<0.001	MFAP5	-0.493	<0.001
BUB1B	0.709	<0.001	COLEC12	-0.491	<0.001
CCNB2	0.699	<0.001	EPAS1	-0.488	<0.001
KIF18B	0.693	<0.001	NRP2	-0.479	<0.001
CCNA2	0.688	<0.001	SH3PXD2A	-0.478	<0.001
MELK	0.685	<0.001	CPQ	-0.478	<0.001
UHRF1	0.685	<0.001	SLCO2B1	-0.474	<0.001
CASC5	0.684	<0.001	LIX1L	-0.473	<0.001

基因	相关系数	P值	基因	相关系数	P值
NCAPG2	0.73	<0.001	PXDC1	-0.535	<0.001
FANCI	0.724	<0.001	YPEL5	-0.51	<0.001
DBF4	0.717	<0.001	MFAP5	-0.493	<0.001
BUB1B	0.709	<0.001	COLEC12	-0.491	<0.001
CCNB2	0.699	<0.001	EPAS1	-0.488	<0.001
KIF18B	0.693	<0.001	NRP2	-0.479	<0.001
CCNA2	0.688	<0.001	SH3PXD2A	-0.478	<0.001
MELK	0.685	<0.001	CPQ	-0.478	<0.001
UHRF1	0.685	<0.001	SLCO2B1	-0.474	<0.001
CASC5	0.684	<0.001	LIX1L	-0.473	<0.001

生物学过程	基因数	P值	涉及基因（仅列出部分）
细胞周期	68	<0.001	ANAPC1，ANAPC11，ANAPC4，ANAPC5，ANAPC7，ATR，BUB1，BUB1B，BUB3，CCNA2，CCNB1，CCNB2，CCNE1，CCNE2，CDC20，CDC23，CDC25A，CDC25B，CDC25C，CDC6，CDC7，CDK1，CDK2，CDK4
剪接体	66	<0.001	ALYREF，AQR，BUD31，CCDC12，CHERP，DHX15，EFTUD2，EIF4A3，HNRNPA1，HNRNPK，HNRNPM，HNRNPU，ISY1，LSM2，LSM3，LSM4，LSM5，LSM6，LSM7，LSM8，MAGOHB，NCBP1，PHF5A，PPIH，PRPF31
RNA转运	75	<0.001	EIF4G1，EIF5B，GEMIN5，GEMIN6，GEMIN7，KPNB1，MAGOHB，NCBP1，NDC1，NUP107，NUP133，NUP155 NUP188
DNA复制	27	<0.001	DNA2，FEN1，LIG1，MCM2，MCM3，MCM4，MCM5，MCM6，MCM7，PCNA，POLA1，POLA2，POLD1，POLD2，POLD3，POLE3，PRIM1
核糖体合成	41	<0.001	CSNK2A2，CSNK2B，DROSHA，FBL，GAR1，GNL2，GTPBP4，HEATR1，IMP3，IMP4，LOC81691，LSG1，MDN1，MPHOSPH10，NAT10，NHP2
蛋白酶体	29	<0.001	POMP，PSMA1，PSMA2，PSMA3，PSMA4，PSMA5，PSMA7，PSMB1，PSMB10，PSMB2，PSMB3，PSMB4，PSMB5，PSMB6，PSMC2
嘧啶代谢	47	<0.001	CAD，CTPS1，DCK，DCTPP1，DHODH，DPYD，DTYMK，DUT，ENTPD1，NME1，NME5，NT5E，PNP，PNPT1，POLA1，POLD2
嘌呤代谢	69	<0.001	ADCY7，ADPRM，ADSL，AK2，AMPD3，APRT，ATIC，CECR1，DCK，DGUOK，ENPP1，ENTPD1，GART，GMPS，HDDC3
范可尼贫血相关通路	25	<0.001	ATR，BLM，BRCA1，BRCA2，BRIP1，EME1，ERCC1，FANCA，FANCB，FANCD2，FANCE，FANCG，FANCI，FANCL，RAD51，RMI1
碱基切除修复	18	<0.001	APEX1，APEX2，FEN1，LIG1，MBD4，NEIL3，PARP1，PARP2，PCNA，POLD1，POLD2，POLD3，POLE，POLE2，POLE3，TDG，UNG，XRCC1

生物学过程	基因数	P值	涉及基因（仅列出部分）
细胞周期	68	<0.001	ANAPC1，ANAPC11，ANAPC4，ANAPC5，ANAPC7，ATR，BUB1，BUB1B，BUB3，CCNA2，CCNB1，CCNB2，CCNE1，CCNE2，CDC20，CDC23，CDC25A，CDC25B，CDC25C，CDC6，CDC7，CDK1，CDK2，CDK4
剪接体	66	<0.001	ALYREF，AQR，BUD31，CCDC12，CHERP，DHX15，EFTUD2，EIF4A3，HNRNPA1，HNRNPK，HNRNPM，HNRNPU，ISY1，LSM2，LSM3，LSM4，LSM5，LSM6，LSM7，LSM8，MAGOHB，NCBP1，PHF5A，PPIH，PRPF31
RNA转运	75	<0.001	EIF4G1，EIF5B，GEMIN5，GEMIN6，GEMIN7，KPNB1，MAGOHB，NCBP1，NDC1，NUP107，NUP133，NUP155 NUP188
DNA复制	27	<0.001	DNA2，FEN1，LIG1，MCM2，MCM3，MCM4，MCM5，MCM6，MCM7，PCNA，POLA1，POLA2，POLD1，POLD2，POLD3，POLE3，PRIM1
核糖体合成	41	<0.001	CSNK2A2，CSNK2B，DROSHA，FBL，GAR1，GNL2，GTPBP4，HEATR1，IMP3，IMP4，LOC81691，LSG1，MDN1，MPHOSPH10，NAT10，NHP2
蛋白酶体	29	<0.001	POMP，PSMA1，PSMA2，PSMA3，PSMA4，PSMA5，PSMA7，PSMB1，PSMB10，PSMB2，PSMB3，PSMB4，PSMB5，PSMB6，PSMC2
嘧啶代谢	47	<0.001	CAD，CTPS1，DCK，DCTPP1，DHODH，DPYD，DTYMK，DUT，ENTPD1，NME1，NME5，NT5E，PNP，PNPT1，POLA1，POLD2
嘌呤代谢	69	<0.001	ADCY7，ADPRM，ADSL，AK2，AMPD3，APRT，ATIC，CECR1，DCK，DGUOK，ENPP1，ENTPD1，GART，GMPS，HDDC3
范可尼贫血相关通路	25	<0.001	ATR，BLM，BRCA1，BRCA2，BRIP1，EME1，ERCC1，FANCA，FANCB，FANCD2，FANCE，FANCG，FANCI，FANCL，RAD51，RMI1
碱基切除修复	18	<0.001	APEX1，APEX2，FEN1，LIG1，MBD4，NEIL3，PARP1，PARP2，PCNA，POLD1，POLD2，POLD3，POLE，POLE2，POLE3，TDG，UNG，XRCC1

生物学过程	基因数	P值	Go Path编号
RNA结合	612	<0.001	3 723
RNA-poly(A)结合	489	<0.001	44 822
有丝分裂细胞周期	420	<0.001	278
细胞周期	503	<0.001	22 402
细胞器形成	1 347	<0.001	43 233
细胞周期	624	<0.001	7 049
细胞核部分形成	1 227	<0.001	44 428
细胞核内腔形成	1 122	<0.001	31 981
细胞器形成	2 200	<0.001	44 446
细胞器形成	2 237	<0.001	44 422

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