AUTHOR=Zheng Ji-Na , Li Yang , Yan Yue-Mei , Shi Hui , Zou Tian-Tian , Shao Wen-Qi , Wang Qiang 

TITLE=Identification and Validation of Key Genes Associated With Systemic Sclerosis-Related Pulmonary Hypertension

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00816

DOI=10.3389/fgene.2020.00816

ISSN=1664-8021

ABSTRACT=<p>Systemic sclerosis-associated with pulmonary arterial hypertension (SSc-PAH) is still a major cause of SSc related deaths. Early diagnosis and prompt treatment are crucial to reduce the mortality of patients with SSc-PAH. To screen the candidate biomarkers and potential therapeutic targets for SSc-PAH, we analyzed the data set (GSE33463 and GSE19617) for confirming key genes in peripheral blood mononuclear cells from SSc-PAH patients. A total of 105 SSc patients from gene expression omnibus (GEO) were included as discovery cohort (<italic>n</italic> = 69) and duplication cohort (<italic>n</italic> = 36) for screening hub genes by weighted gene co-expression network analysis (WGCNA). Furthermore, an independent validation cohort (<italic>n</italic> = 40), including healthy controls, SSc and SSc-PAH patients, was used for further validation by quantitative real-time polymerase chain reaction. The results showed that four key genes, including <italic>IFIT2</italic>, <italic>IFIT3</italic>, <italic>RSAD2</italic>, and <italic>PARP14</italic>, may serve as potential biomarkers in SSc-PAH. Also, they could be independent risk factors for SSc-PAH. In conclusion, the four key genes can be expected to become the potential therapeutic targets and early biomarkers for accurate therapy and diagnosis of SSc-PAH in the future, which also provides promising insights into the pathogenesis of SSc-PAH at the molecular level.</p>