Bioinformatics analysis and significance of key genes for oxaliplatin resistance in colorectal cancer

doi:10.3877/cma.j.issn.1674-0793.2020.05.007

Abstract

Abstract:

Objective

To identify the gene signatures and pathways associated with oxaliplatin (OXA) resistance in colorectal cancer (CRC).

Methods

The gene expression profile of GSE76092 was analyzed from the Gene Expression Omnibus (GEO) database. Via GEO2R tool, differentially expressed genes (DEGs) between OXA-sensitive and OXA-resistant cell lines of CRC were sorted. Then the DAVID online tool was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway. Next, protein-protein interaction (PPI) networks were constructed by STRING and modified by Cytoscape. The hub genes were selected via MCODE plugin and the survival analysis was performed on the GEPIA. Finally, the miRWalk was used to predict the gene-related miRNAs.

Results

A total of 474 DEGs were obtained. The DEGs-related GO and KEGG pathways were identified and the PPI networks were built. Among them, 15 hub genes were screened out, 7 of which were significantly involved in NF-kappa B signaling pathway and Chemokine signaling pathway. The survival analysis of the 7 key genes indicated that CXCL8, IL-1β and PTGS2 expression levels were associated with overall survival. Finally, hsa-miR-6893-5p, hsa-miR-7851-3p and hsa-miR-96-3p were predicted as the core miRNAs.

Conclusion

On the basis of bioinformatical methods, key genes and pathways in OXA-resistant CRC were identified, which could provide a deeper understanding of underlying mechanisms of OXA resistance in CRC.

Key words: Colorectal Neoplasms, Oxaliplatin, Resistance, Bioinformatics analysis

Jianbo Xu, Xingyu Zhou, Qinqin Xie, Xinde Ou, Jinning Ye, Jianjun Peng, Hui Wu. Bioinformatics analysis and significance of key genes for oxaliplatin resistance in colorectal cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2020, 14(05): 349-354.

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Figures/Tables 7

References 20

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类型	描述	P值	计数
分子功能	氧化还原酶活性	9.67×10^-5	15
?	醛基酮还原酶（NADP）活性	2.26×10^-4	5
?	醛脱氢酶（NAD）活性	3.80×10^-4	5
?	WW结构域结合	4.50×10^-4	6
?	氧化还原酶活性	5.99×10^-4	5
细胞成分	细胞外空间	1.44×10^-9	64
?	细胞外囊泡	2.00×10^-9	105
?	顶质膜	1.35×10^-3	16
?	侵卵膜	6.25×10^-3	3
?	微绒毛	6.83×10^-3	6
生物学过程	氧化还原过程	1.53×10^-5	31
?	细胞迁移的正调控	4.98×10^-5	15
?	细胞增殖的负调控	1.61×10^-4	22
?	柔红霉素代谢过程	5.22×10^-4	4
?	阿霉素代谢	5.22×10^-4	4
KEGG通路	组氨酸代谢	1.23×10^-3	5
?	代谢通路	4.86×10^-3	41
?	酪氨酸代谢	7.04×10^-3	5
?	甘油脂代谢	8.82×10^-3	6
?	色氨酸代谢	11.29×10^-3	5

类型	描述	P值	计数
分子功能	氧化还原酶活性	9.67×10^-5	15
?	醛基酮还原酶（NADP）活性	2.26×10^-4	5
?	醛脱氢酶（NAD）活性	3.80×10^-4	5
?	WW结构域结合	4.50×10^-4	6
?	氧化还原酶活性	5.99×10^-4	5
细胞成分	细胞外空间	1.44×10^-9	64
?	细胞外囊泡	2.00×10^-9	105
?	顶质膜	1.35×10^-3	16
?	侵卵膜	6.25×10^-3	3
?	微绒毛	6.83×10^-3	6
生物学过程	氧化还原过程	1.53×10^-5	31
?	细胞迁移的正调控	4.98×10^-5	15
?	细胞增殖的负调控	1.61×10^-4	22
?	柔红霉素代谢过程	5.22×10^-4	4
?	阿霉素代谢	5.22×10^-4	4
KEGG通路	组氨酸代谢	1.23×10^-3	5
?	代谢通路	4.86×10^-3	41
?	酪氨酸代谢	7.04×10^-3	5
?	甘油脂代谢	8.82×10^-3	6
?	色氨酸代谢	11.29×10^-3	5

?	基因名	英文全称	中文全称
上调基因	CXCL8	C-X-C motif chemokine ligand 8	C-X-C基序趋化因子配体8
?	CXCL1	C-X-C motif chemokine ligand 1	C-X-C基序趋化因子配体1
?	NMU	neuromedin U	神经调节素U
?	S1PR2	sphingosine-1-phosphate receptor 2	鞘氨醇-1-磷酸受体2
?	GPSM1	G protein signaling modulator 1	G蛋白信号传导调节剂1
?	OXGR1	oxoglutarate receptor 1	草酸谷氨酸受体1
?	IL-1β	interleukin 1β	白介素1β
?	PLAU	plasminogen activator, urokinase	纤溶酶原激活剂、尿激酶
?	PTGS2	prostaglandin-endoperoxide synthase 2	前列腺素-内过氧化物合酶2
?	SPP1	secreted phosphoprotein 1	分泌型磷蛋白1
?	TIMP2	tissue inhibitor of metalloproteinase 2	金属蛋白酶2组织抑制剂
下调基因	GNAI1	G protein subunit alpha i1	G蛋白亚基alpha i1
?	PF4	platelet factor 4	血小板因子4
?	ADRA2A	adrenoceptor alpha 2A	肾上腺素受体2A
?	PLAUR	plasminogen activator, urokinase receptor	纤溶酶原激活剂、尿激酶受体

?	基因名	英文全称	中文全称
上调基因	CXCL8	C-X-C motif chemokine ligand 8	C-X-C基序趋化因子配体8
?	CXCL1	C-X-C motif chemokine ligand 1	C-X-C基序趋化因子配体1
?	NMU	neuromedin U	神经调节素U
?	S1PR2	sphingosine-1-phosphate receptor 2	鞘氨醇-1-磷酸受体2
?	GPSM1	G protein signaling modulator 1	G蛋白信号传导调节剂1
?	OXGR1	oxoglutarate receptor 1	草酸谷氨酸受体1
?	IL-1β	interleukin 1β	白介素1β
?	PLAU	plasminogen activator, urokinase	纤溶酶原激活剂、尿激酶
?	PTGS2	prostaglandin-endoperoxide synthase 2	前列腺素-内过氧化物合酶2
?	SPP1	secreted phosphoprotein 1	分泌型磷蛋白1
?	TIMP2	tissue inhibitor of metalloproteinase 2	金属蛋白酶2组织抑制剂
下调基因	GNAI1	G protein subunit alpha i1	G蛋白亚基alpha i1
?	PF4	platelet factor 4	血小板因子4
?	ADRA2A	adrenoceptor alpha 2A	肾上腺素受体2A
?	PLAUR	plasminogen activator, urokinase receptor	纤溶酶原激活剂、尿激酶受体

类型	描述	计数	P值	基因名
KEGG	NF-κB信号通路	4	3.00×10^-4	PTGS2、CXCL8、IL-1β、PLAU
?	趋化因子信号通路	4	2.73×10^-3	CXCL1、GNAI1、CXCL8、PF4
?	军团菌病	3	3.18×10^-3	CXCL1、CXCL8、IL-1β
?	NOD样受体信号通路	3	3.42×10^-3	CXCL1、CXCL8、IL-1β
?	细胞因子与细胞因子受体的相互作用	4	5.82×10^-3	CXCL1、CXCL8、IL-1β、PF4
GO	调节细胞增殖	5	1.15×10^-5	CXCL1、PTGS2、CXCL8、PF4、PLAU
?	细胞外空间	7	5.23×10^-5	CXCL1、CXCL8、IL-1β、PF4、TIMP2、PLAU、SPP1
?	CXCR结合	3	8.12×10^-5	CXCL1、CXCL8、PF4
?	免疫反应	4	8.47×10^-4	CXCL1、CXCL8、IL-1β、PF4
?	趋化因子介导的信号通路	3	9.44×10^-4	CXCL1、CXCL8、PF4

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