Computational identification of novel potential genetic pathogenesis and otherwise biomarkers in acute liver allograft rejection
Cheng Zhang,
Jun-Ze Chen,
Kun Dong,
Yong-Yuan Jian,
Kai-Yong Huang,
Rui-Ling Su,
Xue-Lin Tan,
Guan-Dou Yuan,
Yu-yan Lan,
Song-Qing He,
Chun-Qiang Dong
Affiliations
Cheng Zhang
Department of Organ Transplantation, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Jun-Ze Chen
Department of Organ Transplantation, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Kun Dong
Department of Organ Transplantation, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Yong-Yuan Jian
Department of Organ Transplantation, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Kai-Yong Huang
Department of Organ Transplantation, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Rui-Ling Su
Department of Organ Transplantation, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Xue-Lin Tan
Department of Organ Transplantation, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Guan-Dou Yuan
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi, China
Yu-yan Lan
Department of Anesthesiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Song-Qing He
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi, China; Corresponding author. the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Chun-Qiang Dong
Department of Organ Transplantation, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Corresponding author. the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Acute cellular rejection (ACR) is a prevalent postoperative complication following liver transplantation (LT), exhibiting an increasing incidence of morbidity and mortality. However, the molecular mechanisms of ACR following LT remain unclear. To explore the genetic pathogenesis and identify biomarkers of ACR following LT, three relevant Gene Expression Omnibus (GEO) datasets consisting of data on ACR or non-ACR patients after LT were comprehensively investigated by computational analysis. A total of 349 upregulated and 260 downregulated differentially expressed genes (DEGs) and eight hub genes (ISG15, HELZ2, HNRNPK, TIAL1, SKIV2L2, PABPC1, SIRT1, and PPARA) were identified. Notably, HNRNPK, TIAL1, and PABPC1 exhibited the highest predictive potential for ACR with AUCs of 0.706, 0.798, and 0.801, respectively. KEGG analysis of hub genes revealed that ACR following LT was predominately associated with ferroptosis, protein processing in the endoplasmic reticulum, complement and coagulation pathways, and RIG-I/NOD/Toll-like receptor signaling pathway. According to the immune cell infiltration analysis, γδT cells, NK cells, Tregs, and M1/M2-like macrophages had the highest levels of infiltration. Compared to SIRT1, ISG15 was positively correlated with γδT cells and M1-like macrophages but negatively correlated with NK cells, CD4+ memory T cells, and Tregs. In conclusion, this study identified eight hub genes and their potential pathways, as well as the immune cells involved in ACR following LT with the greatest levels of infiltration. These findings provide a new direction for future research on the underlying mechanism of ACR following LT.