AUTHOR=Xu Wenqing , Deng Mei , Meng Xiapei , Sun Xuebiao , Tao Xincao , Wang Dingyi , Zhang Shuai , Zhen Yanan , Liu Xiaopeng , Liu Min 

TITLE=The alterations in molecular markers and signaling pathways in chronic thromboembolic pulmonary hypertension, a study with transcriptome sequencing and bioinformatic analysis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.961305

DOI=10.3389/fcvm.2022.961305

ISSN=2297-055X

ABSTRACT=Background: At present, the alterations of molecular markers and signaling pathways in chronic thromboembolic pulmonary hypertension (CTEPH) remain unclear. We aimed to compare the difference of molecular markers and signaling pathways in CTEPH patients and healthy people with transcriptome sequencing and bioinformatics analysis.
Methods: We prospectively included 26 patients with CTEPH and 35 sex- and age-matched healthy volunteers as control. We extracted RNA from whole blood samples to construct the library. Then, qualified libraries were sequenced using PE100 strategy on BGIseq platform. Subsequently, the DESeq2 package in R was used to screen differentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) of 7 CTEPH patients and 5 healthy volunteers. Afterwards, we performed functional enrichment and protein-protein interaction analysis of DEmRNAs. We also performed lncRNA-mRNA co-expression analysis and lncRNA-miRNA-mRNA network construction. In addition, we performed diagnostic analysis on the GSE130391 dataset. Finally, we performed in vitro validation of genes in 19 CTEPH patients and 30 healthy volunteers.
Results: Gender and age between CTEPH patients and healthy controls, between sequencing group and in vitro validation group were comparable. A total of 437 DEmRNAs and 192 DElncRNAs were obtained. Subsequently, 205 pairs of interacting DEmRNAs and 232 pairs of lncRNA-mRNA relationship were obtained. DEmRNAs were significantly enriched in chemokine signaling pathway, metabolic pathways, arachidonic acid metabolism and MAPK signaling pathway. Only one regulation pathway of SOBP-has-miR-320b-LINC00472 was found through ceRNA network construction. In diagnostic analysis, the area under curve (AUC) of LINC00472, PIK3R6, SCN3A and TCL6 respectively were 0.964, 0.893, 0.750 and 0.732. 
Conclusion: The identification of alterations of molecules and pathways may provide further research directions on pathogenesis of CTEPH. And LINC00472, PIK3R6, SCN3A and TCL6 may as the potential gene markers in CTEPH.