Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a rare cardiovascular disease with very high mortality rate. The currently available therapeutic strategies, which improve symptoms, cannot fundamentally reverse the condition. Thus, new therapeutic strategies need to be established. Our research analyzed thr...
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doaj-997777b17ec44a5083345605c316850e2021-09-26T00:13:03ZengMDPI AGGenes2073-44252021-08-01121339133910.3390/genes12091339Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial HypertensionAoqi Li0Jin He1Zhe Zhang2Sibo Jiang3Yun Gao4Yuchun Pan5Huanan Wang6Lenan Zhuang7Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Animal Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaInstitute of Genetics and Reproduction, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaZhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaZhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaInstitute of Genetics and Reproduction, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaInstitute of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaZhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaPulmonary arterial hypertension (PAH) is a rare cardiovascular disease with very high mortality rate. The currently available therapeutic strategies, which improve symptoms, cannot fundamentally reverse the condition. Thus, new therapeutic strategies need to be established. Our research analyzed three microarray datasets of lung tissues from human PAH samples retrieved from the Gene Expression Omnibus (GEO) database. We combined two datasets for subsequent analyses, with the batch effects removed. In the merged dataset, 542 DEGs were identified and the key module relevant to PAH was selected using WGCNA. GO and KEGG analyses of DEGs and the key module indicated that the pre-ribosome, ribosome biogenesis, centriole, ATPase activity, helicase activity, hypertrophic cardiomyopathy, melanoma, and dilated cardiomyopathy pathways are involved in PAH. With the filtering standard (|MM| > 0.95 and |GS| > 0.90), 70 hub genes were identified. Subsequently, five candidate marker genes (<i>CDC5L</i>, <i>AP3B1</i>, <i>ZFYVE16</i>, <i>DDX46</i>, and <i>PHAX</i>) in the key module were found through overlapping with the top thirty genes calculated by two different methods in CytoHubb. Two of them (<i>CDC5L</i> and <i>DDX46</i>) were found to be significantly upregulated both in the merged dataset and the validating dataset in PAH patients. Meanwhile, expression of the selected genes in lung from PAH chicken measured by qRT-PCR and the ROC curve analyses further verified the potential marker genes’ predictive value for PAH. In conclusion, <i>CDC5L</i> and <i>DDX46</i> may be marker genes and potential therapeutic targets for PAH.https://www.mdpi.com/2073-4425/12/9/1339WGCNApulmonary arterial hypertensionhub genes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aoqi Li Jin He Zhe Zhang Sibo Jiang Yun Gao Yuchun Pan Huanan Wang Lenan Zhuang |
spellingShingle |
Aoqi Li Jin He Zhe Zhang Sibo Jiang Yun Gao Yuchun Pan Huanan Wang Lenan Zhuang Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial Hypertension Genes WGCNA pulmonary arterial hypertension hub genes |
author_facet |
Aoqi Li Jin He Zhe Zhang Sibo Jiang Yun Gao Yuchun Pan Huanan Wang Lenan Zhuang |
author_sort |
Aoqi Li |
title |
Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial Hypertension |
title_short |
Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial Hypertension |
title_full |
Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial Hypertension |
title_fullStr |
Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial Hypertension |
title_full_unstemmed |
Integrated Bioinformatics Analysis Reveals Marker Genes and Potential Therapeutic Targets for Pulmonary Arterial Hypertension |
title_sort |
integrated bioinformatics analysis reveals marker genes and potential therapeutic targets for pulmonary arterial hypertension |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2021-08-01 |
description |
Pulmonary arterial hypertension (PAH) is a rare cardiovascular disease with very high mortality rate. The currently available therapeutic strategies, which improve symptoms, cannot fundamentally reverse the condition. Thus, new therapeutic strategies need to be established. Our research analyzed three microarray datasets of lung tissues from human PAH samples retrieved from the Gene Expression Omnibus (GEO) database. We combined two datasets for subsequent analyses, with the batch effects removed. In the merged dataset, 542 DEGs were identified and the key module relevant to PAH was selected using WGCNA. GO and KEGG analyses of DEGs and the key module indicated that the pre-ribosome, ribosome biogenesis, centriole, ATPase activity, helicase activity, hypertrophic cardiomyopathy, melanoma, and dilated cardiomyopathy pathways are involved in PAH. With the filtering standard (|MM| > 0.95 and |GS| > 0.90), 70 hub genes were identified. Subsequently, five candidate marker genes (<i>CDC5L</i>, <i>AP3B1</i>, <i>ZFYVE16</i>, <i>DDX46</i>, and <i>PHAX</i>) in the key module were found through overlapping with the top thirty genes calculated by two different methods in CytoHubb. Two of them (<i>CDC5L</i> and <i>DDX46</i>) were found to be significantly upregulated both in the merged dataset and the validating dataset in PAH patients. Meanwhile, expression of the selected genes in lung from PAH chicken measured by qRT-PCR and the ROC curve analyses further verified the potential marker genes’ predictive value for PAH. In conclusion, <i>CDC5L</i> and <i>DDX46</i> may be marker genes and potential therapeutic targets for PAH. |
topic |
WGCNA pulmonary arterial hypertension hub genes |
url |
https://www.mdpi.com/2073-4425/12/9/1339 |
work_keys_str_mv |
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