Upregulation of the key biomarker kinesin family member 20A (KIF20A) is associated with pulmonary artery hypertension

Linqing Li; Qi Xue; Minhao Zhang; Zhanneng Yang; Dong Wang; Gaoliang Yan; Yong Qiao; Chengchun Tang; Rui Zhang

doi:10.1016/j.ygeno.2023.110705

Upregulation of the key biomarker kinesin family member 20A (KIF20A) is associated with pulmonary artery hypertension

Genomics. 2023 Sep;115(5):110705. doi: 10.1016/j.ygeno.2023.110705. Epub 2023 Sep 12.

Authors

Linqing Li¹, Qi Xue², Minhao Zhang², Zhanneng Yang², Dong Wang², Gaoliang Yan², Yong Qiao², Chengchun Tang³, Rui Zhang⁴

Affiliations

¹ Zhongda Hospital, Southeast University, Department of Cardiology, China; Linyi People's Hospital, 210009 Nanjing, China.
² Zhongda Hospital, Southeast University, Department of Cardiology, China.
³ Zhongda Hospital, Southeast University, Department of Cardiology, China. Electronic address: tangchengchun@hotmail.com.
⁴ Zhongda Hospital, Southeast University, Department of Cardiology, China. Electronic address: zhangruiSEU@163.com.

PMID: 37703933
DOI: 10.1016/j.ygeno.2023.110705

Abstract

Objective: Pulmonary artery hypertension (PAH) is a complex, fatal disease with limited treatments. This study aimed to investigate possible key targets in PAH through bioinformatics.

Methods: GSE144274 were obtained from Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) between idiopathic pulmonary hypertension (IPAH) and healthy subjects were identified and analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed, and a protein-protein interaction (PPI) network was constructed using STRING. The hub genes were identified by MCODE method. The expression levels of hub genes were validated in vitro and in vivo models. Finally, the ROC analysis was performed based on the level of hub genes in clinical plasma samples.

Results: A total of 363 DEGs were identified. GO analysis on these DEGs were mainly enriched in cell division, inflammatory response, among others. In the KEGG pathways analysis, DEGs mainly involved in cytokine-cytokine receptor interaction, rheumatoid arthritis, and IL-17 signaling pathways were enriched. The DEGs were analyzed with the STRING for PPI network analysis, and 62 hub genes were identified by MCODE. Finally, 6 central genes, KIF18B, SPC25, DLGAP5, KIF20A, CEP55 and ANLN, were screened out due to their novelty role in PAH. The expression of KIF20A was validated to be significantly upregulated both in the lung tissue of hypoxia-induced pulmonary hypertension (HPH) mice and proliferative PASMCs. Additionally, KIF20A levels is evelated in PAH plasma and the area under the curve (AUC) to identify PAH was 0.8591 for KIF20A.

Conclusion: The level of KIF20A elevates during the progression of PAH, which suggestes it could be a potential diagnostic and therapeutic target for the PAH.

Keywords: Bioinformatics; Biomarker; KIF20A; Pulmonary artery hypertension; RNA-seq.