Pyroptosis-related signatures predict immune characteristics and prognosis in IPF

Yijun He; Tingting Yao; Yan Zhang; Lingzhi Long; Guoliang Jiang; Xiangyu Zhang; Xin Lv; Yuanyuan Han; Xiaoyun Cheng; Mengyu Li; Mao Jiang; Zhangzhe Peng; Lijian Tao; Jie Meng

Heliyon (Jan 2024)

Pyroptosis-related signatures predict immune characteristics and prognosis in IPF

Yijun He,
Tingting Yao,
Yan Zhang,
Lingzhi Long,
Guoliang Jiang,
Xiangyu Zhang,
Xin Lv,
Yuanyuan Han,
Xiaoyun Cheng,
Mengyu Li,
Mao Jiang,
Zhangzhe Peng,
Lijian Tao,
Jie Meng

Affiliations

Yijun He: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, China
Tingting Yao: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, China
Yan Zhang: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, China
Lingzhi Long: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, China
Guoliang Jiang: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, China
Xiangyu Zhang: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, China
Xin Lv: Hunan Key Laboratory of Organ Fibrosis, Changsha, China; Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China
Yuanyuan Han: Hunan Key Laboratory of Organ Fibrosis, Changsha, China; Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China
Xiaoyun Cheng: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, China
Mengyu Li: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, China
Mao Jiang: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China
Zhangzhe Peng: Hunan Key Laboratory of Organ Fibrosis, Changsha, China; Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China; National International Collaborative Research Center for Medical Metabolomics, Changsha, China
Lijian Tao: Hunan Key Laboratory of Organ Fibrosis, Changsha, China; Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China; National International Collaborative Research Center for Medical Metabolomics, Changsha, China
Jie Meng: Department of Pulmonary and Critical Care Medicine, Third Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Organ Fibrosis, Changsha, China; National International Collaborative Research Center for Medical Metabolomics, Changsha, China; Corresponding author. Third Xiangya Hospital, Central South University, No.138 Tongzipo Road, Changsha 410013, China.

Journal volume & issue: Vol. 10, no. 1
p. e23683

Abstract

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The purpose of this work was to use integrated bioinformatics analysis to screen for pyroptosis-related genes (PRGs) and possible immunological phenotypes linked to the development and course of IPF. Transcriptome sequencing datasets GSE70866, GSE47460 and GSE150910 were obtained from GEO database. From the GSE70866 database, 34 PRGs with differential expression were found in IPF as compared to healthy controls. In addition, a diagnostic model containing 4 genes PRGs (CAMP, MKI67, TCEA3 and USP24) was constructed based on LASSO logistic regression. The diagnostic model showed good predictive ability to differentiate between IPF and healthy, with ROC-AUC ranging from 0.910 to 0.997 in GSE70866 and GSE150910 datasets. Moreover, based on a combined cohort of the Freiburg and the Siena cohorts from GSE70866 dataset, we identified ten PRGs that might predict prognosis for IPF. We constructed a prognostic model that included eight PRGs (CLEC5A, TREM2, MMP1, IRF2, SEZ6L2, ADORA3, NOS2, USP24) by LASSO Cox regression and validated it in the Leuven cohort. The risk model divided IPF patients from the combined cohort into high-risk and low-risk subgroups. There were significant differences between the two subgroups in terms of IPF survival and GAP stage. There is a close correlation between leukocyte migration, plasma membrane junction, and poor prognosis in a high-risk subgroup. Furthermore, a high-risk score was associated with more plasma cells, activated NK cells, monocytes, and activated mast cells. Additionally, we identified HDAC inhibitors in the cMAP database that might be therapeutic for IPF. To summarize, pyroptosis and its underlying immunological features are to blame for the onset and progression of IPF. PRG-based predictive models and drugs may offer new treatment options for IPF.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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