Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic Data
Background. Sepsis is a leading cause of mortality in intensive care units worldwide. A better understanding of the blood systems response to sepsis should expedite the identification of biomarkers for early diagnosis and therapeutic interventions. Methods. We analyzed microarray studies whose data...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/984825 |
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| author | Jie Ma Chuanxi Chen Andreas S. Barth Chris Cheadle Xiangdong Guan Li Gao |
| author_facet | Jie Ma Chuanxi Chen Andreas S. Barth Chris Cheadle Xiangdong Guan Li Gao |
| author_sort | Jie Ma |
| collection | DOAJ |
| description | Background. Sepsis is a leading cause of mortality in intensive care units worldwide. A better understanding of the blood systems response to sepsis should expedite the identification of biomarkers for early diagnosis and therapeutic interventions. Methods. We analyzed microarray studies whose data is available from the GEO repository and which were performed on the whole blood of septic patients and normal controls. Results. We identified 6 cohorts consisting of 450 individuals (sepsis = 323, control = 127) providing genome-wide messenger RNA (mRNA) expression data. Through meta-analysis we found the “Lysosome” and “Cytoskeleton” pathways were upregulated in human sepsis patients relative to controls, in addition to previously known signaling pathways (including MAPK, TLR). The key regulatory genes in the “Lysosome” pathway include lysosomal acid hydrolases (e.g., protease cathepsin A, D) as well as the major (LAMP1, 2) and minor (SORT1, LAPTM4B) membrane proteins. In contrast, pathways related to “Ribosome”, “Spliceosome” and “Cell adhesion molecules” were found to be downregulated, along with known pathways for immune dysfunction. Overall, our study revealed distinct mRNA activation profiles and protein-protein interaction networks in blood of human sepsis. Conclusions. Our findings suggest that aberrant mRNA expression in the lysosome and cytoskeleton pathways may play a pivotal role in the molecular pathobiology of human sepsis. |
| format | Article |
| id | doaj-art-b6ed15ed1f494637aac6fdcab2f61132 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-b6ed15ed1f494637aac6fdcab2f611322025-02-03T01:07:46ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/984825984825Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic DataJie Ma0Chuanxi Chen1Andreas S. Barth2Chris Cheadle3Xiangdong Guan4Li Gao5Division of Allergy & Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USADivision of Allergy & Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USADivision of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADivision of Allergy & Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USADepartment of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, ChinaDivision of Allergy & Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USABackground. Sepsis is a leading cause of mortality in intensive care units worldwide. A better understanding of the blood systems response to sepsis should expedite the identification of biomarkers for early diagnosis and therapeutic interventions. Methods. We analyzed microarray studies whose data is available from the GEO repository and which were performed on the whole blood of septic patients and normal controls. Results. We identified 6 cohorts consisting of 450 individuals (sepsis = 323, control = 127) providing genome-wide messenger RNA (mRNA) expression data. Through meta-analysis we found the “Lysosome” and “Cytoskeleton” pathways were upregulated in human sepsis patients relative to controls, in addition to previously known signaling pathways (including MAPK, TLR). The key regulatory genes in the “Lysosome” pathway include lysosomal acid hydrolases (e.g., protease cathepsin A, D) as well as the major (LAMP1, 2) and minor (SORT1, LAPTM4B) membrane proteins. In contrast, pathways related to “Ribosome”, “Spliceosome” and “Cell adhesion molecules” were found to be downregulated, along with known pathways for immune dysfunction. Overall, our study revealed distinct mRNA activation profiles and protein-protein interaction networks in blood of human sepsis. Conclusions. Our findings suggest that aberrant mRNA expression in the lysosome and cytoskeleton pathways may play a pivotal role in the molecular pathobiology of human sepsis.http://dx.doi.org/10.1155/2015/984825 |
| spellingShingle | Jie Ma Chuanxi Chen Andreas S. Barth Chris Cheadle Xiangdong Guan Li Gao Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic Data Mediators of Inflammation |
| title | Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic Data |
| title_full | Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic Data |
| title_fullStr | Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic Data |
| title_full_unstemmed | Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic Data |
| title_short | Lysosome and Cytoskeleton Pathways Are Robustly Enriched in the Blood of Septic Patients: A Meta-Analysis of Transcriptomic Data |
| title_sort | lysosome and cytoskeleton pathways are robustly enriched in the blood of septic patients a meta analysis of transcriptomic data |
| url | http://dx.doi.org/10.1155/2015/984825 |
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