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使用CX3CR1相关免疫浸润基因的综合模型对丙型肝炎病毒诱导的早期肝硬化进行预后评估。

Prognostic assessment of early-stage liver cirrhosis induced by HCV using an integrated model of CX3CR1-associated immune infiltration genes.

作者信息

Cai Haozheng, Zhang Jing, Chen Chuwen, Shen Junyi, Zhang Xiaoyun, Peng Wei, Li Chuan, Lv Haopeng, Wen Tianfu

机构信息

Division of Liver Surgery, Department of General Surgery, West China Hospital, Si Chuan University, Chengdu, 610041, China.

Division of Biliary Tract, Department of General Surgery, West China Hospital, Si Chuan University, Chengdu, China.

出版信息

Sci Rep. 2025 Jan 13;15(1):1771. doi: 10.1038/s41598-024-80422-1.

Abstract

Chemokine (C-X3-C motif) Receptor 1 (CX3CR1) primarily mediates the chemotaxis and adhesion of immune cells. However, its role in hepatitis C virus (HCV)-induced early-stage liver cirrhosis remains unexplored. GSE15654 was downloaded from the GEO database. The Cox regression model, CIBERSORT, and LASSO technique were utilized to identify CX3CR1-associated immune infiltration genes (IIGs). Surgical resection samples were collected for verification, including 3 healthy controls (HC), 4 individuals with HCV-induced hepatic cirrhosis, and 3 with HCV-induced liver failure. High CX3CR1 expression correlated with worse prognosis in early-stage cirrhosis. CX3CR1-associated IIGs, namely ACTIN4, CD1E, TMCO1, and WSF1, were identified, showing specific expression in the livers of individuals with post-hepatic cirrhosis and liver failure compared to HC. LOC400499 and MTHFD2 were elevated in individuals with liver failure in comparison to those with hepatocirrhosis. Notably, high infiltration of plasma cells and low infiltration of monocytes were predictive of poor prognosis in early-stage cirrhosis. The combined risk model predicted that high expression of CX3CR1-associated IIGs and increased infiltration of plasma cells were associated with unfavorable prognosis in individuals with HCV-induced early-stage liver cirrhosis. The developed combined risk model effectively predicted the prognosis of these individuals.

摘要

趋化因子(C-X3-C基序)受体1(CX3CR1)主要介导免疫细胞的趋化作用和黏附。然而,其在丙型肝炎病毒(HCV)诱导的早期肝硬化中的作用仍未得到探索。从基因表达综合数据库(GEO数据库)下载了GSE15654。利用Cox回归模型、CIBERSORT和套索技术来识别与CX3CR1相关的免疫浸润基因(IIG)。收集手术切除样本进行验证,包括3名健康对照者(HC)、4名HCV诱导的肝硬化患者和3名HCV诱导的肝衰竭患者。CX3CR1高表达与早期肝硬化患者较差的预后相关。识别出与CX3CR1相关的IIG,即肌动蛋白4(ACTIN4)、CD1E、跨膜卷曲螺旋蛋白1(TMCO1)和Wolfram综合征1(WSF1),与HC相比,这些基因在肝后性肝硬化和肝衰竭患者的肝脏中呈现特异性表达。与肝硬化患者相比,肝衰竭患者中LOC400499和亚甲基四氢叶酸脱氢酶2(MTHFD2)升高。值得注意的是,浆细胞的高浸润和单核细胞的低浸润预示着早期肝硬化患者预后不良。联合风险模型预测,CX3CR1相关IIG的高表达和浆细胞浸润增加与HCV诱导的早期肝硬化患者的不良预后相关。所建立的联合风险模型有效地预测了这些患者预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2b/11725579/97d9da18f0f8/41598_2024_80422_Fig1_HTML.jpg

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