N‐myc and STAT interactor correlates with severity and prognosis in acute‐on‐chronic liver failure of hepatitis B virus

Abstract

Background and Aim Hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF) is characterized by acute deterioration of chronic liver disease with excessive inflammation. N‐myc and STAT interactor (NMI), an inflammation‐mediated protein, involves in various inflammatory‐related diseases, but the role of NMI in development and prognosis in HBV‐ACLF remains to be elucidated. Methods Serum NMI from healthy controls (HCs, n = 20), chronic hepatitis B (CHB, n = 50) patients, and HBV‐ACLF patients (n = 50) was determined using ELISA. NMI from peripheral blood mononuclear cells and liver was confirmed using quantitative real‐time polymerase chain reaction, Western blot, and immunofluorescence. Results Serum NMI was increased 1.9‐fold or 2.2‐fold from HBV‐ACLF patients compared with that from HCs (P < 0.01) or CHB patients (P < 0.01). Consistently, NMI from peripheral blood mononuclear cells was upregulated significantly from HBV‐ACLF patients compared with that from HCs and CHB patients at mRNA and protein levels. Hepatic NMI from HBV‐ACLF patients was 2.8‐fold higher than that from HCs. Serum NMI was correlated with Model for End‐stage Liver Disease, Chronic Liver Failure Consortium ACLF score, and ACLF grades. In contrast, serum NMI was significantly decreased in HBV‐ACLF ameliorated patients during follow‐up, whereas serum NMI was sustained at high levels in non‐ameliorated patients. Elevated serum NMI (≥ 198.5 pg/mL) was correlated with poor survival rate of HBV‐ACLF patients. Using receiver operating characteristics curves, it was suggested that serum NMI was a potential biomarker in predicting 3‐month mortality of HBV‐ACLF patients. Conclusions Our study highlights the potential role of NMI in assessing the development and prognosis of HBV‐ACLF.

N-Myc and STAT Interactor is a Novel Biomarker of Severity in Community-Acquired Pneumonia: A Cohort Study

“…Wu et al showed that NMI expression in human lung A549 cells was upregulated after H3N2 SIV infection [40]. NMI levels also elevated in serum and liver tissue of patients with hepatitis B virus-related acute-tochronic liver failure and the concentrations of NMI decreased when in convalescent stage of disease [19]. Our current results showed that the expression of NMI in both serum and BALF was signi cantly increased in CAP and that NMI levels were positively correlated with mortality and ICU admission.…”

“…Previous studies have already shown that NMI is associated with various in ammatory diseases [18,19,39,40].…”

“…N-myc and STAT interactor (NMI), a binding partner of N-myc and c-Myc oncogenes, acts as a transcriptional regulator in multiple signaling pathways in the nucleus [16,17]. It has been linked to tumor growth and progression as well as participating with macrophages in the in ammatory response [18,19]. NMI plays a key role in proin ammatory cytokine interleukin (IL)-32ε-mediated apoptosis by inhibiting Wnt/β-catenin signaling and activating cmyc-mediated apoptosis to regulate the host defense against pathogens such as Mycobacterium tuberculosis [20].…”

Bioinformatics analyses of significant genes, related pathways, and candidate diagnostic biomarkers and molecular targets in SARS-CoV-2/COVID-19

“…Enriched genes such as A2M [ Chen et al, 2010 ], CLEC5A [ Teng et al, 2016 ], ZBP1 [ T. Zhang et al, 2020 ], PLSCR1 [ Luo et al, 2018 ], FKBP5 [ Hao et al, 2020 ], FPR2 [ Schloer et al, 2019 ], CD226 [ Redlberger-Fritz et al, 2019 ], PTPN22 [ Crabtree et al, 2016 ], CEACAM1 [ Ye et al, 2018 ], CD80 [ Lumsden et al, 2000 ] CD86 [ Lumsden et al, 2000 ], CD68 [ McGuinness et al, 2000 ], MLKL (mixed lineage kinase domain like pseudokinase) [ Gaba et al, 2019 ] and TRIM28 [ Krischuns et al, 2018 ] were liable for progression of influenza viral infection, but these genes may be associated with development of SARS-CoV-2 infection. Enriched genes such as LILRB2 [ Alaoui et al, 2018 ], SERPINB9 [ Mangan et al, 2017 ], FCGR3A [ Poonia et al, 2010 ], MICB (MHC class I polypeptide-related sequence B) [ Libraty et al, 2014 ], CD274 [ Jeong et al, 2008 ], SLAMF7 [ O'Connell et al, 2019 ], CMPK2 [ El-Diwany et al, 2018 ], IFIT5 [ Rohaim et al, 2018 ], APOBEC3A [ Berger et al, 2011 ], APOBEC3F [ Burdick et al, 2013 ], HAVCR2 [ Sironi et al, 2014 ], NMI (N-myc and STAT interactor) [ Xiong et al, 2019 ], CD96 [ Eriksson et al, 2012 ], CLEC2D [ Varaden et al, 2019 ], CD53 [ Tippett et al, 2013 ] and CD69 [ Yong et al, 2017 ] were linked with progression of various viral infections, but these genes may be key for progression of SARS-CoV-2 infection. Enriched genes such as CD209 [ Amraei et al, 2020 ], APOL1 [ Wu et al, 2020 ], PARP14 [ Webb and Saad, 2020 ], TF (transferrin) [ McLaughlin et al, 2020 ], ACE2 [ Yan et al, 2020 ], FLT1 [ Giardini et al, 2020 ] and BRCA2 [ Singh and Bharara Singh, 2020 ] were involved in advancement of SARS-CoV-2 infection.…”

Acute-on-Chronic Liver Failure From Chronic-Hepatitis-B, Who Is the Behind Scenes

“…Even though several biomarkers such as microRNA (hsa-miR-21-5p), the inflammation-mediated protein (N-myc and ATAT interactor, NMI) may be useful novel biomarkers of ACLF ( Ding et al, 2015 ; Xiong et al, 2019 ), more appropriate, accurate, and early indicators are still needed owing to the rapid progression of ACLF. It is well known that ALCF patients have higher complexity and diversity within the BCP/PC region of HBV, indicating distinct quasispecies characteristics among ALCF patients ( Chen L. et al, 2013 ).…”