Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients
The global coronavirus disease 2019 (COVID-19) pandemic has lasted for over 2 years now and has already caused millions of deaths. In COVID-19, leukocyte pyroptosis has been previously associated with both beneficial and detrimental effects, so its role in the development of this disease remains con...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.888661/full |
| _version_ | 1818195590274613248 |
|---|---|
| author | Yingkui Tang Peidong Zhang Qiuyu Liu Luyang Cao Jingsong Xu Jingsong Xu |
| author_facet | Yingkui Tang Peidong Zhang Qiuyu Liu Luyang Cao Jingsong Xu Jingsong Xu |
| author_sort | Yingkui Tang |
| collection | DOAJ |
| description | The global coronavirus disease 2019 (COVID-19) pandemic has lasted for over 2 years now and has already caused millions of deaths. In COVID-19, leukocyte pyroptosis has been previously associated with both beneficial and detrimental effects, so its role in the development of this disease remains controversial. Using transcriptomic data (GSE157103) of blood leukocytes from 126 acute respiratory distress syndrome patients (ARDS) with or without COVID-19, we found that COVID-19 patients present with enhanced leukocyte pyroptosis. Based on unsupervised clustering, we divided 100 COVID-19 patients into two clusters (PYRcluster1 and PYRcluster2) according to the expression of 35 pyroptosis-related genes. The results revealed distinct pyroptotic patterns associated with different leukocytes in these PYRclusters. PYRcluster1 patients were in a hyperinflammatory state and had a worse prognosis than PYRcluster2 patients. The hyperinflammation of PYRcluster1 was validated by the results of gene set enrichment analysis (GSEA) of proteomic data (MSV000085703). These differences in pyroptosis between the two PYRclusters were confirmed by the PYRscore. To improve the clinical treatment of COVID-19 patients, we used least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model based on differentially expressed genes between PYRclusters (PYRsafescore), which can be applied as an effective prognosis tool. Lastly, we explored the upstream transcription factors of different pyroptotic patterns, thereby identifying 112 compounds with potential therapeutic value in public databases. |
| first_indexed | 2024-12-12T01:20:36Z |
| format | Article |
| id | doaj.art-fa4545e0743e4ed2900d14d7ae98797e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T01:20:36Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fa4545e0743e4ed2900d14d7ae98797e2022-12-22T00:43:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.888661888661Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 PatientsYingkui Tang0Peidong Zhang1Qiuyu Liu2Luyang Cao3Jingsong Xu4Jingsong Xu5State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Critical Care Medicine, Yongchuan Hospital, Chongqing Medical University, Chongqing, ChinaGuangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, ChinaGuangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, ChinaThe global coronavirus disease 2019 (COVID-19) pandemic has lasted for over 2 years now and has already caused millions of deaths. In COVID-19, leukocyte pyroptosis has been previously associated with both beneficial and detrimental effects, so its role in the development of this disease remains controversial. Using transcriptomic data (GSE157103) of blood leukocytes from 126 acute respiratory distress syndrome patients (ARDS) with or without COVID-19, we found that COVID-19 patients present with enhanced leukocyte pyroptosis. Based on unsupervised clustering, we divided 100 COVID-19 patients into two clusters (PYRcluster1 and PYRcluster2) according to the expression of 35 pyroptosis-related genes. The results revealed distinct pyroptotic patterns associated with different leukocytes in these PYRclusters. PYRcluster1 patients were in a hyperinflammatory state and had a worse prognosis than PYRcluster2 patients. The hyperinflammation of PYRcluster1 was validated by the results of gene set enrichment analysis (GSEA) of proteomic data (MSV000085703). These differences in pyroptosis between the two PYRclusters were confirmed by the PYRscore. To improve the clinical treatment of COVID-19 patients, we used least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model based on differentially expressed genes between PYRclusters (PYRsafescore), which can be applied as an effective prognosis tool. Lastly, we explored the upstream transcription factors of different pyroptotic patterns, thereby identifying 112 compounds with potential therapeutic value in public databases.https://www.frontiersin.org/articles/10.3389/fimmu.2022.888661/fullCOVID-19pyroptosisleukocytesprognosis modeltranscription factors |
| spellingShingle | Yingkui Tang Peidong Zhang Qiuyu Liu Luyang Cao Jingsong Xu Jingsong Xu Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients Frontiers in Immunology COVID-19 pyroptosis leukocytes prognosis model transcription factors |
| title | Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients |
| title_full | Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients |
| title_fullStr | Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients |
| title_full_unstemmed | Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients |
| title_short | Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients |
| title_sort | pyroptotic patterns in blood leukocytes predict disease severity and outcome in covid 19 patients |
| topic | COVID-19 pyroptosis leukocytes prognosis model transcription factors |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.888661/full |
| work_keys_str_mv | AT yingkuitang pyroptoticpatternsinbloodleukocytespredictdiseaseseverityandoutcomeincovid19patients AT peidongzhang pyroptoticpatternsinbloodleukocytespredictdiseaseseverityandoutcomeincovid19patients AT qiuyuliu pyroptoticpatternsinbloodleukocytespredictdiseaseseverityandoutcomeincovid19patients AT luyangcao pyroptoticpatternsinbloodleukocytespredictdiseaseseverityandoutcomeincovid19patients AT jingsongxu pyroptoticpatternsinbloodleukocytespredictdiseaseseverityandoutcomeincovid19patients AT jingsongxu pyroptoticpatternsinbloodleukocytespredictdiseaseseverityandoutcomeincovid19patients |