Identification of transcriptomics biomarkers for the early prediction of the prognosis of septic shock from pneumopathies

Shi, Songchang; Pan, Xiaobin; Feng, Hangwei; Zhang, Shujuan; Shu, Shi; Lin, Wei

doi:10.1186/s12879-021-06888-w

Cited by 7 publications

(3 citation statements)

References 35 publications

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“…Furthermore, according the microarray analyses by Ye et al [12], THBS1 was downregulated in SAT patients and could be served as the prognostic marker for sepsis with pneumonia. Shi et al also con rmed the downregulation pattern of THBS1 in septic shock and showed it could serve as differentiation factor with high AUC of 0.889 [13]. Here, we established the mouse SAT model by LPS induction, and found that THBS1 is signi cantly in LPS challenged mice decreased compared to the control mice, which is preliminary con rmed that the involvement of THBS1 in the presence of SAT.…”

Section: Discussionsupporting

confidence: 74%

WITHDRAWN: Identification of platelets related THBS1 as a critical gene in sepsis related thrombocytopenia via an integrated bioinformatic analysis

Liu

2022

Preprint

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Objective To explore the role of platelet related differentially expressed genes (plt-DEGs) THBS1 in sepsis through integrated bioinformatics analyses and in vivo mouse model. Methods Four GEO derived datasets and platelet related genes were downloaded and intersection was performed to obtain the plt-DEGs in sepsis, followed by GO and KEGG analysis, PPI network, prognostic model establishment and immune cell infiltration analyses. Finally, an LPS-challenged mouse model was established for THBS1 quantification. Results A total of 85 plt-DEGs were obtained, including 56 up- and 29 down-regulated plt-DEGs. Among them, 16 genes showed a significant correlation with survival statue and 10 genes, including PLA2G4A, GNAQ, PIK3CB, LHFPL2, SCCPDH, PRKCD, VEGFA, CCNA2, PRKDC and SLC9A3R1, were found with prognostic prediction ability in sepsis. Moreover, these 10 genes were found correlated with the immune cell infiltration and 9 genes except SLC9A3R1 showed upregulated trend in sepsis. Significantly decreased level of THBS1 was found in LPS-challenged mice and THBS1 was found to be involved in platelet degranulation, response to drug and activation of MAPK activity Conclusions plt-DEGs was found correlated with survival statue, immune cell infiltration and could be used as prognostic marker in Sepsis. Plt-DEG THBS1 could be further studied sepsis thrombocytopenia.

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Section: Discussionsupporting

confidence: 74%

WITHDRAWN: Identification of platelets related THBS1 as a critical gene in sepsis related thrombocytopenia via an integrated bioinformatic analysis

Liu

2022

Preprint

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“…However, in dataset, since no differential genes were screened out with adj. p .val < 0.05 ( Table S4 ), and the p -value < 0.05 is also allowed in the bioinformatics analysis ( Cheng et al, 2021 ; Shi et al, 2021 ), we use p .val < 0.05 & log |FC | > 1.5 as the cutoff. Performance of the model was evaluated through timeROC package (v0.4).…”

Section: Methodsmentioning

confidence: 99%

A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma

Zhang,

Liu,

Gao

et al. 2023

PeerJ

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Background There is a heterogenous clinical response following chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC). Therefore, we aimed to study signaling pathway genes that affect CRT sensitivity and prognosis. Methods Gene expression analyses were performed in the GEO and TCGA datasets. A immunohistochemistry (IHC) analysis was performed in pretreatment biopsies. Results MMP13 was found to be highly expressed in the “Pathologic Complete Response (pCR)” and “Complete Remission (CR)” and “Alive” groups. Th17 cells and MMP9/13 showed a negative correlation in immune infiltration analysis. In GSEA analysis, IL-4 and IL-13 signaling pathways were highly enriched in patients exhibiting high MMP expression in pCR and CR groups. IHC results suggested higher MMP13 & IL-4 and lower IL-17A & RORC expression in the CR group compared to the <CR (CR not achieved) group. Survival analyses further indicated that the prognosis was worse in the high IL-17A group (p = 0.046, HR = 2.15). Next, a prognostic model was established. In the training cohort, AUCs for the 1/2/3/4/5-year OS were all greater than 0.70. In the two validation cohorts, 1-year AUCs were also >0.70, and the model could well distinguish high-risk and low-risk subgroups. Conclusion The above results may provide guidance for developing novel treatment and prognostic strategies in ESCC patients.

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“…Omics, cell surface marker expression, immune cell profiles, and biomarker analysis have been utilized to classify the immune status of sepsis patients (10,12,(14)(15)(16)(17)(18)(27)(28)(29). However, no studies have examined how these omic changes correlate with fundamental mechanisms of neutrophil-mediated damage in sepsis, specifically how heterogeneous neutrophil-endothelial cell interactions differentially impact vascular barrier disruption and neutrophil migration across the endothelium into vital organs.…”

Section: Introductionmentioning

confidence: 99%

Distinct functional neutrophil phenotypes in sepsis patients correlate with disease severity

Yang,

Langston,

Prosniak

et al. 2024

Front. Immunol.

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PurposeSepsis is a clinical syndrome defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is a highly heterogeneous syndrome with distinct phenotypes that impact immune function and response to infection. To develop targeted therapeutics, immunophenotyping is needed to identify distinct functional phenotypes of immune cells. In this study, we utilized our Organ-on-Chip assay to categorize sepsis patients into distinct phenotypes using patient data, neutrophil functional analysis, and proteomics.MethodsFollowing informed consent, neutrophils and plasma were isolated from sepsis patients in the Temple University Hospital ICU (n=45) and healthy control donors (n=7). Human lung microvascular endothelial cells (HLMVEC) were cultured in the Organ-on-Chip and treated with buffer or cytomix ((TNF/IL-1β/IFNγ). Neutrophil adhesion and migration across HLMVEC in the Organ-on-Chip were used to categorize functional neutrophil phenotypes. Quantitative label-free global proteomics was performed on neutrophils to identify differentially expressed proteins. Plasma levels of sepsis biomarkers and neutrophil extracellular traps (NETs) were determined by ELISA.ResultsWe identified three functional phenotypes in critically ill ICU sepsis patients based on ex vivo neutrophil adhesion and migration patterns. The phenotypes were classified as: Hyperimmune characterized by enhanced neutrophil adhesion and migration, Hypoimmune that was unresponsive to stimulation, and Hybrid with increased adhesion but blunted migration. These functional phenotypes were associated with distinct proteomic signatures and differentiated sepsis patients by important clinical parameters related to disease severity. The Hyperimmune group demonstrated higher oxygen requirements, increased mechanical ventilation, and longer ICU length of stay compared to the Hypoimmune and Hybrid groups. Patients with the Hyperimmune neutrophil phenotype had significantly increased circulating neutrophils and elevated plasma levels NETs.ConclusionNeutrophils and NETs play a critical role in vascular barrier dysfunction in sepsis and elevated NETs may be a key biomarker identifying the Hyperimmune group. Our results establish significant associations between specific neutrophil functional phenotypes and disease severity and identify important functional parameters in sepsis pathophysiology that may provide a new approach to classify sepsis patients for specific therapeutic interventions.

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Identification of transcriptomics biomarkers for the early prediction of the prognosis of septic shock from pneumopathies

Cited by 7 publications

References 35 publications

WITHDRAWN: Identification of platelets related THBS1 as a critical gene in sepsis related thrombocytopenia via an integrated bioinformatic analysis

WITHDRAWN: Identification of platelets related THBS1 as a critical gene in sepsis related thrombocytopenia via an integrated bioinformatic analysis

A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma

Distinct functional neutrophil phenotypes in sepsis patients correlate with disease severity

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