PMID- 35272172 OWN - NLM STAT- MEDLINE DCOM- 20220510 LR - 20220510 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 107 DP - 2022 Jun TI - Characterization of immune-related genes andimmune infiltration features for early diagnosis, prognosis and recognition of immunosuppression in sepsis. PG - 108650 LID - S1567-5769(22)00134-5 [pii] LID - 10.1016/j.intimp.2022.108650 [doi] AB - Among the body systems, the immune system plays a fundamental role in the pathophysiology of sepsis. The effects of immunogenomic and immune cell infiltration in sepsis were still not been systematically understood. Based on modified Lasso penalized regression and RF, 8 DEIRGs (ADM, CX3CR1, DEFA4, HLA-DPA1, MAPK14, ORM1, RETN, and SLPI) were combined to construct an IRG classifier. In the discovery cohort, IRG classifier exhibited superior diagnostic efficacy and performed better in predicting mortality than clinical characteristics or MARS/SRS endotypes. Encouragingly, similar results were observed in the ArrayExpress databases. The use of hydrocortisone in IRG high-risk subgroup was associated with increased risk of mortality. In IRG low-risk phenotypes, NK cells, T helper cells, and infiltrating lymphocyte (IL) are significantly richer, while T cells regulatory (Tregs) and myeloid-derived suppressor cells (MDSC) are more abundant in IRG high-risk phenotypes. IRG score were significantly negatively correlated with Cytokine cytokine receptor interaction (CCR) and human leukocyte antigen (HLA). Between the IRG subgroups, the expression levels of several cytokines (IL-10, IFNG, TNF) were significantly different, and IRG score was significantly positively correlated with ratio of IL-10/TNF. Results of qRT-PCR validated that higher expression level of ADM, DEFA4, MAPK14, ORM1, RETN, and SLPI as well as lower expression level of CX3CR1 and HLA-DPA1 in sepsis samples compared to control sample. A diagnostic and prognostic model, namely IRG classifier, was established based on 8 IRGs that is closely correlated with responses to hydrocortisone and immunosuppression status and might facilitate personalized counseling for specific therapy. CI - Copyright (c) 2022. Published by Elsevier B.V. FAU - Lu, Jianhai AU - Lu J AD - Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, Guangdong Province, PR China. FAU - Chen, Rui AU - Chen R AD - Department of Medical Intensive Care Unit, General Hospital of Southern Theater Command, PLA, Guangzhou 510010, Guangdong Province, PR China. FAU - Ou, Yangpeng AU - Ou Y AD - Department of Oncology, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou, 516000, Guangdong Province, PR China. FAU - Jiang, Qianhua AU - Jiang Q AD - Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, Guangdong Province, PR China. FAU - Wang, Liping AU - Wang L AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, PR China. FAU - Liu, Genglong AU - Liu G AD - Department of Pathology, The Third Affiliated Hospital of Guangdong Medical University (Longjiang Hospital of Shunde District), Foshan 528318, Guangdong Province, PR China. FAU - Liu, Yayun AU - Liu Y AD - Department of Endocrinology, GuiYang Huaxi District People's Hospital. Guiyang 550025, Guizhou Province, PR China. FAU - Yang, Ben AU - Yang B AD - Department of Burn Surgery, Huizhou Municipal Central Hospital, Huizhou 516000, Guangdong Province, PR China. FAU - Zhou, Zhujiang AU - Zhou Z AD - Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, Guangdong Province, PR China. FAU - Zuo, Liuer AU - Zuo L AD - Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, Guangdong Province, PR China. Electronic address: 13500276597@163.com. FAU - Chen, Zhen AU - Chen Z AD - Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, Guangdong Province, PR China. Electronic address: jeanyz@foxmail.com. LA - eng PT - Journal Article DEP - 20220307 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Biomarkers, Tumor) RN - 130068-27-8 (Interleukin-10) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14) RN - WI4X0X7BPJ (Hydrocortisone) SB - IM MH - Biomarkers, Tumor/genetics MH - Early Diagnosis MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Hydrocortisone MH - Immunosuppression Therapy MH - Interleukin-10/genetics MH - *Mitogen-Activated Protein Kinase 14/genetics MH - Prognosis MH - *Sepsis/diagnosis/genetics MH - Tumor Microenvironment OTO - NOTNLM OT - Immune infiltration OT - Immune-related genes OT - Immunosuppression OT - Model OT - Sepsis EDAT- 2022/03/11 06:00 MHDA- 2022/05/11 06:00 CRDT- 2022/03/10 20:14 PHST- 2021/12/10 00:00 [received] PHST- 2022/01/23 00:00 [revised] PHST- 2022/02/20 00:00 [accepted] PHST- 2022/03/11 06:00 [pubmed] PHST- 2022/05/11 06:00 [medline] PHST- 2022/03/10 20:14 [entrez] AID - S1567-5769(22)00134-5 [pii] AID - 10.1016/j.intimp.2022.108650 [doi] PST - ppublish SO - Int Immunopharmacol. 2022 Jun;107:108650. doi: 10.1016/j.intimp.2022.108650. Epub 2022 Mar 7.