Construction of co-expression network and target analysis of Stanford type A aortic dissection associated gene KIF20A

doi:10.3877/cma.j.issn.2095-1221.2024.05.006

Abstract

Abstract:

Objective

To further explore the pathogenesis of Stanford Type A aortic dissection and screen potential novel molecular biomarkers by identifying differentially expressed genes in Stanford Type A aortic dissection and constructing a gene co-expression network.

Methods

Gene expression arrays of Stanford Type A aortic dissection were obtained from the GEO database. The R limma package was used to screen differentially expressed mRNAs（ P＜ 0.05，|log₂FC|＞ 1）. Key differentially expressed genes involved in the pathogenesis of aortic dissection were selected for comprehensive investigation. Subsequently， the expression of key differentially expressed genes and the coded protein were validated by quantitative real-time PCR and Western blot in vascular wall tissues from Stanford Type A aortic dissection patients and control group. The gene co-expression network of the selected gene was constructed by bioinformatic analysis； To clarify the biological functions of the co-expression network， the function and pathway enrichment analysis of the co-expressed genes were performed by ggplot2 package in R language. Further， a protein- protein interaction （PPI） network of these co-expressed genes was constructed to identify the genes interacting with the hub gene directly and validate their correlation. By integrating gene co-expression and PPI networks， we established the gene interaction mechanisms relevant to aortic dissection and explored the specific molecular mechanisms underlying its pathogenesis. Independent sample t test was used for comparison between the two groups.

Results

A total of 969 differentially expressed genes were identified in Stanford Type A aortic dissection through the application of the WALD test. Based on co-expression network analysis， we selected the upregulated gene KIF20A for further investigation in aortic dissection， and subsequently validated its elevated expression levels in clinical samples. There were 53 genes in the co-expression network of KIF20A， with 20 genes positively correlated and 33 negatively correlated with KIF20A expression. Functional enrichment analysis of this network was mainly enriched in biological processes such as polarity regulation of epithelial cells，mitochondrial function， and arginine and proline metabolism. Further analysis showed that CDK1 directly interacted with KIF20A， and the expression levels of the two genes were positively correlated（r = 0.83，P＜ 0.001）.

Conclusion

KIF20A is significantly elevated in Stanford Type A aortic dissection tissues and potentially interacts with CDK1， regulating the expression of a series of genes affecting biological processes such as polarity establishment and regulation of epithelium and tissue，mitochondrial function， and thus mediating the occurrence and development of aortic dissection.

Key words: Stanford type A aortic dissection, Gene expression profiles, KIF20A, Gene co-expression networks, Interaction mechanisms

Tingyu Wang, Lianbo Shao, Shan Liu, Zhenya Shen. Construction of co-expression network and target analysis of Stanford type A aortic dissection associated gene KIF20A[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(05): 303-312.

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URL: https://zhxbygxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-1221.2024.05.006

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Figures/Tables 17

References 40

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基因	序列（5'→3'）	预期扩增产物长度（bp）
KIF20A	上游TGCTGTCCGATGACGATGTC	82
	下游AGGTTCTTGCGTACCACAGAC
18s	上游GTAACCCGTTGAACCCCATT	151
	下游CCATCCAATCGGTAGTAGCG

基因	序列（5'→3'）	预期扩增产物长度（bp）
KIF20A	上游TGCTGTCCGATGACGATGTC	82
	下游AGGTTCTTGCGTACCACAGAC
18s	上游GTAACCCGTTGAACCCCATT	151
	下游CCATCCAATCGGTAGTAGCG

	对照组（n=3）	疾病组（n=3）	P值
年龄（岁）	58±2.08	59±5.51	0.833
性别（男/女）	2/1	3/0	-
主动脉直径（mm）	38.4±3.21	45.87±4.20	0.022
高血压	2/3	2/3	-
动脉粥样硬化	0	0	-
糖尿病	0	0	-

	对照组（n=3）	疾病组（n=3）	P值
年龄（岁）	58±2.08	59±5.51	0.833
性别（男/女）	2/1	3/0	-
主动脉直径（mm）	38.4±3.21	45.87±4.20	0.022
高血压	2/3	2/3	-
动脉粥样硬化	0	0	-
糖尿病	0	0	-

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