Transcriptional Profiling Identified the Key Genes and Pathways of the Pterygium

Abstract

Background: Pterygium results from the variety of biological pathways which is involved in the formation of ocular surface diseases. However, the accurate pathogenesis of pterygium is still unclear. Our study focused on the gene expression profiling signatures to better understand the potential mechanisms of pterygium. Methods: RNA-sequence experiment was applied into the 8 clinical pterygium tissues and 10 normal conjunctival tissues. To identify the hub gene for the development of pterygium, we further conducted the weighted gene co-expression network analysis (WGCNA). qRT-PCR and western blotting were utilized to validate the dysregulation of key hub genes in the independent subjects. Findings: 339 differentially expressed genes (DEGs) were obtained that reached the statistical significance with the p-value < 0.05. Among them, 200 DEGs were up-regulated which mainly involved in extracellular matrix and cell adhesion or migration while the 139 down-regulated genes were enriched into the endocrine and inflammation. For the WGCNA analysis, 5 modules were assigned from the DEGs expression profiling and the biological functions of each module were verified the previously published GO terms including the ECM-receptor interaction, PI3K-Akt signaling pathway and endoplasmic reticulum (ER) related pathway.The 5 hub genes with higher connectivity in each module as well as the ER stress genes were validated dysregulated expression in the independent cohort samples. Interpretation: Our integrated omics-level WGCNA analysis suggested novel insights into the potential regulatory mechanisms of pterygium. The identified hub genes involved in ER stress may provide an important reference for further research on the molecular biology of pterygium. Funding Statement: This study was supported by the Scientific Research Foundation of Shanghai Municipal Commission of Health and Family Planning (201840336); the Natural Science Foundation of Shanghai (17ZR1427100), the National Natural Science Foundation of China (81300771, 31871281, 81400397), The Project of Key Disciplines of Medicine in Yangpu District of Shanghai (YP16ZA02) and the Shanghai Jiao Tong Univ Liberal Arts and Sciences Cross-Disciplinary Project (YG2014QN13) Declaration of Interests: No authors of this paper have any conflicts of interest. Ethics Approval Statement: The research protocol was approved by the institutional review board of Yangpu Hospital and all study participants wrote the informed consent. The study was carried out in accordance with the declaration of Helsinki.