Chronic Liver
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Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 180
Author(s):  
Pil-Soo Sung ◽  
Chang-Min Kim ◽  
Jung-Hoon Cha ◽  
Jin-Young Park ◽  
Yun-Suk Yu ◽  
...  

Innate and adaptive immune responses are critically associated with the progression of fibrosis in chronic liver diseases. In this study, we aim to identify a unique immune-related gene signature representing advanced liver fibrosis and to reveal potential therapeutic targets. Seventy-seven snap-frozen liver tissues with various chronic liver diseases at different fibrosis stages (1: n = 12, 2: n = 12, 3: n = 25, 4: n = 28) were subjected to expression analyses. Gene expression analysis was performed using the nCounter PanCancer Immune Profiling Panel (NanoString Technologies, Seattle, WA, USA). Biological meta-analysis was performed using the CBS Probe PINGSTM (CbsBioscience, Daejeon, Korea). Using non-tumor tissues from surgically resected specimens, we identified the immune-related, five-gene signature (CHIT1_FCER1G_OSM_VEGFA_ZAP70) that reliably differentiated patients with low- (F1 and F2) and high-grade fibrosis (F3 and F4; accuracy = 94.8%, specificity = 91.7%, sensitivity = 96.23%). The signature was independent of all pathological and clinical features and was independently associated with high-grade fibrosis using multivariate analysis. Among these genes, the expression of inflammation-associated FCER1G, OSM, VEGFA, and ZAP70 was lower in high-grade fibrosis than in low-grade fibrosis, whereas CHIT1 expression, which is associated with fibrogenic activity of macrophages, was higher in high-grade fibrosis. Meta-analysis revealed that STAT3, a potential druggable target, highly interacts with the five-gene signature. Overall, we identified an immune gene signature that reliably predicts advanced fibrosis in chronic liver disease. This signature revealed potential immune therapeutic targets to ameliorate liver fibrosis.


2022 ◽  
Vol 000 (000) ◽  
pp. 000-000
Author(s):  
Lili Wu ◽  
Jieyang Jin ◽  
Taicheng Zhou ◽  
Yuankai Wu ◽  
Xinhua Li ◽  
...  

Hepatology ◽  
2022 ◽  
Author(s):  
Sumedha Gunewardena ◽  
Ian Huck ◽  
Chad Walesky ◽  
Dakota Robarts ◽  
Steven Weinman ◽  
...  

2022 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jasmohan S. Bajaj ◽  
Jacqueline G. O'Leary ◽  
Jennifer C. Lai ◽  
Florence Wong ◽  
Millie D. Long ◽  
...  

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