Identification of the immune infiltration and biomarkers in ulcerative colitis based on liquid-liquid phase
Zhixing Hong1, Shilin Fang2, Haihang Nie3,4,5
1Department of Emergency Medicine, The First People's Hospital of Linping District, Hangzhou, China.
Abstract:
Liquid-liquid phase separation (LLPS) associates with immune infiltration in multiple diseases. Nonetheless, the role of LLPS-related genes (LLPS-RGs) in immune infiltration of ulcerative colitis (UC) is still elusive. We identified the hub LLPS-RGs (DE-LLPS-RGs) (HSPB3, SLC16A1, TRIM22, SRI, PLEKHG6, GBP1, PADI2) by machine learning algorithms. Hub genes were screened that displayed high prediction accuracy of UC patients. Both the microarray and scRNA-seq datasets showed a strong correlation with immune cell infiltration and cytokines, especially GBP1, TRIM22, SRI. And qRT-PCR analysis showed that GBP1 play a pro-inflammatory role in UC. Two distinct clusters were identified, in which cluster A displayed higher immune infiltration level compared with the cluster B. The top targeted biological pathways of two clusters were distinct, glutamate receptor antagonist ranked top for cluster A while HDAC inhibitor ranked top in cluster B. External cohort and UC cell model validation indicated the similar immune infiltration levels, gene expression and cytokine expression patterns. We determined the seven high accuracy diagnostic genes of UC patients and provide a new perspective on immunoregulation in UC pathogenesis. And suggest patient stratification and candidate targets for precision treatment based on hub genes screened.
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