An integrative multi-cohort transcriptomic study reveals cell cycle- and adhesion-related hub genes as diagnostic biomarkers for pulmonary arterial hypertension

Jiajia Zou; Guojiao Rao; Xiaomin Hou; Zhifa Zheng; Mengjie Xu; Xian Li; Yan Gao; Yiwei Shi; Xiaojiang Qin

doi:10.1016/j.jbior.2026.101145

An integrative multi-cohort transcriptomic study reveals cell cycle- and adhesion-related hub genes as diagnostic biomarkers for pulmonary arterial hypertension

Adv Biol Regul. 2026 Jan 13:100:101145. doi: 10.1016/j.jbior.2026.101145. Online ahead of print.

Authors

Jiajia Zou¹, Guojiao Rao², Xiaomin Hou³, Zhifa Zheng⁴, Mengjie Xu¹, Xian Li¹, Yan Gao⁵, Yiwei Shi⁶, Xiaojiang Qin⁷

Affiliations

¹ School of Public Health, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, China; Environmental Exposures Vascular Disease Institute, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, China.
² Environmental Exposures Vascular Disease Institute, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, China; Academy of Medical Science, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, China.
³ Environmental Exposures Vascular Disease Institute, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, China; Department of Pharmacology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, China; China Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
⁴ Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, China.
⁵ Department of Foreign Languages, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
⁶ Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China; NHC Key Laboratory of Pneumoconiosis, Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
⁷ School of Public Health, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, China; Environmental Exposures Vascular Disease Institute, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, China; NHC Key Laboratory of Pneumoconiosis, Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China. Electronic address: sph@sxmu.edu.cn.

PMID: 41576688
DOI: 10.1016/j.jbior.2026.101145

Abstract

Pulmonary arterial hypertension (PAH) is a progressive and fatal vascular disorder for which reliable and non-invasive diagnostic biomarkers remain limited. This study aims to screen and verify the hub genes related to PAH by integrating bioinformatics and experimental verification. We analyzed four GEO datasets (GSE117261, GSE24988, GSE53408, GSE113439) to identify differentially expressed genes and co-expressed modules. Functional enrichment analysis revealed the pathways related to vascular smooth muscle contraction and organ development. Protein-protein interaction network analysis screened out 4 hub genes. These genes showed different expression dysfunctions in the training set, an independent validation set and a Single-cell sequencing dataset (GSE33463, GSE228644), and demonstrated good diagnostic value through ROC curve analysis. Crucially, in the nicotine-induced PAH mouse model, RT-qPCR experiments confirmed the significant upregulation of these 4 genes. Our research results have established CDK1, TPX2, IGF1 and VCAM1 as robust polygenic markers related to PAH, providing potential evidence for clarifying their molecular mechanisms and developing non-invasive diagnostic tools.

Keywords: Biomarkers; Hub genes; Nicotine; Pulmonary arterial hypertension.