ITGBL1在代谢功能障碍相关脂肪性肝炎中的表达及与患者预后的相关性分析

肝脏 ›› 2026, Vol. 31 ›› Issue (2): 257-263.

ITGBL1在代谢功能障碍相关脂肪性肝炎中的表达及与患者预后的相关性分析

戴雯, 陈晖, 李自强, 纪易斐, 陆翠华, 黄伟

226001 南通南通市南通大学附属医院消化内科(戴雯,陈晖,纪易斐,陆翠华,黄伟);200025 上海上海交通大学医学院附属瑞金医院感染科(李自强)

收稿日期:2025-03-21 出版日期:2026-02-28 发布日期:2026-04-17
通讯作者: 黄伟,Email:huangweint@ntu.edu.cn
基金资助:
中国博士后科学基金(2022M711719);2023年度王宝恩肝纤维化研究基金(2024029);2021年度天晴肝病研究基金(TQGB20210029)

Expression of ITGBL1 in metabolic dysfunction-associated steatohepatitis and its correlation with patient prognosis

DAI Wen¹, CHEN Hui¹, LI Zi-qiang², JI Yi-fei¹, LU Cui-hua¹, HUANG Wei¹

1. Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, China;
2. Department of Infectious Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China

Received:2025-03-21 Online:2026-02-28 Published:2026-04-17
Contact: HUANG Wei,Email: huangweint@ntu.edu.cn

摘要/Abstract

摘要： 目的揭示ITGBL1在代谢功能障碍相关脂肪性肝炎(MASH)肝纤维化进程中的表达特征,阐明其与纤维化分期及临床预后的相关性。方法基于GEO数据库的MASH患者肝组织转录组数据,应用降维分析观察样本分布特征;对各组间数据进行差异基因表达分析(DEGs),绘制韦恩图寻找交集基因;分析ITGBL1的表达与MASH患者肝纤维化程度之间的相关性;构建受试者工作特征(ROC)曲线评估其分期诊断价值;分析ITGBL1的表达与患者肝组织中免疫细胞浸润的相关性;最后,通过荧光原位杂交技术(FISH)探究ITGBL1 mRNA的细胞定位及表达差异。结果韦恩图显示,ITGBL1基因在各个DEGs组间均共同表达;随着MASH患者肝纤维化程度的加重,ITGBL1 mRNA的表达水平呈显著上升趋势,且其对患者肝纤维化进展方面的预测性能亦显著提升,尤其在F4阶段,AUC值达到0.958(P<0.001,95%CI 3.118~34.769),具有较高的灵敏度(88.9%)和特异度(95.7%);ITGBL1的表达与巨噬细胞M1呈正相关(R=0.468,P<0.0001),与M2呈负相关(R=-0.188,P<0.05)。FISH结果显示,ITGBL1 mRNA在MASH-F2患者肝细胞核内特异性富集(荧光强度较对照组增加3.8倍,P=0.0021)。结论 ITGBL1有望作为MASH肝纤维化进展的新型分子标志物,其动态表达特征对晚期纤维化具有高精度诊断价值。

Abstract: Objective To investigate the dynamic expression of ITGBL1 in metabolic dysfunction-associated steatohepatitis (MASH)-related hepatic fibrosis and elucidate its correlation with fibrosis staging and clinical prognosis. Methods Transcriptomic data from MASH patient liver tissues were retrieved from the GEO database. Dimensionality reduction analysis was performed to visualize sample distribution patterns. Differentially expressed genes (DEGs) across fibrosis stages were identified, and common intersecting genes were screened using Venn diagrams. Correlation analysis was used to evaluate the association between ITGBL1 expression and fibrosis severity. Receiver operating characteristic (ROC) curves were constructed to assess diagnostic efficacy. Immune cell infiltration profiles were analyzed, and fluorescence in situ hybridization (FISH) was used to determine the subcellular localization of ITGBL1 mRNA. Results Venn analysis identified ITGBL1 as a core intersection gene across all DEG groups. ITGBL1 expression exhibited a fibrosis stage-dependent escalation, with optimal diagnostic performance at F4 stage (AUC=0.958, 95% CI: 3.118~34.769; sensitivity=88.9%, specificity=95.7%). ITGBL1 expression was positively correlated with M1 macrophage infiltration (R=0.468, P<0.0001) but negatively correlated with M2 polarization (R=-0.188, P=0.032). FISH confirmed nuclear-specific enrichment of ITGBL1 mRNA in F2-stage hepatocytes (3.8-fold fluorescence intensity increase vs. controls, P=0.0021). Conclusion ITGBL1 serves as a novel molecular biomarker for MASH-related hepatic fibrosis progression, shows high diagnostic accuracy for advanced fibrosis stages.

Key words: Metabolic dysfunction-associated steatohepatitis, ITGBL1, Liver fibrosis, Prognosis, Macrophage polarization

戴雯, 陈晖, 李自强, 纪易斐, 陆翠华, 黄伟. ITGBL1在代谢功能障碍相关脂肪性肝炎中的表达及与患者预后的相关性分析[J]. 肝脏, 2026, 31(2): 257-263.

DAI Wen, CHEN Hui, LI Zi-qiang, JI Yi-fei, LU Cui-hua, HUANG Wei. Expression of ITGBL1 in metabolic dysfunction-associated steatohepatitis and its correlation with patient prognosis[J]. Chinese Hepatolgy, 2026, 31(2): 257-263.

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参考文献

[1] 许耀珑, 赵佳欣, 杨立刚. 非酒精性脂肪性肝病流行现状及危险因素研究进展 [J]. 中国全科医学, 2024, 27(30): 3825-3834.
[2] Targher G, Byrne C D, Tilg H. MASLD: a systemic metabolic disorder with cardiovascular and malignant complications [J]. Gut, 2024, 73(4): 691-702.
[3] Targher G, Tilg H, Byrne C D. Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach [J]. Lancet Gastroenterol Hepatol, 2021, 6(7): 578-588.
[4] Younossi Z, Tacke F, Arrese M, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [J]. Hepatology, 2019, 69(6): 2672-2682.
[5] Singh S, Allen A M, Wang Z, et al. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies [J]. Clin Gastroenterol Hepatol, 2015, 13(4): 643-54.e1-9; quiz e39-40.
[6] Loomba R, Friedman S L, Shulman G I. Mechanisms and disease consequences of nonalcoholic fatty liver disease [J]. Cell, 2021, 184(10): 2537-2564.
[7] Sheka A C, Adeyi O, Thompson J, et al. Nonalcoholic steatohepatitis: a review [J]. JAMA, 2020, 323(12): 1175-1183.
[8] Pulixi E A, Tobaldini E, Battezzati P M, et al. Risk of obstructive sleep apnea with daytime sleepiness is associated with liver damage in non-morbidly obese patients with nonalcoholic fatty liver disease [J]. PLoS One, 2014, 9(4): e96349.
[9] Hammerich L, Tacke F. Hepatic inflammatory responses in liver fibrosis [J]. Nat Rev Gastroenterol Hepatol, 2023, 20(10): 633-646.
[10] Berg R W, Leung E, Gough S, et al. Cloning and characterization of a novel beta integrin-related cDNA coding for the protein TIED ("ten beta integrin EGF-like repeat domains") that maps to chromosome band 13q33: a divergent stand-alone integrin stalk structure [J]. Genomics, 1999, 56(2): 169-178.
[11] Cheli Y, Tulic M K, El Hachem N, et al. ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity [J]. Mol Cancer, 2021, 20(1): 12.
[12] Ye F, Huang W, Xue Y, et al. Serum levels of ITGBL1 as an early diagnostic biomarker for hepatocellular carcinoma with hepatitis B virus infection [J]. J Hepatocell Carcinoma, 2021, 8: 285-300.
[13] Huang W, Yu D, Wang M, et al. ITGBL1 promotes cell migration and invasion through stimulating the TGF-β signalling pathway in hepatocellular carcinoma [J]. Cell Prolif, 2020, 53(7): e12836.
[14] Song X, Xu P, Meng C, et al. lncITPF promotes pulmonary fibrosis by targeting hnRNP-L depending on its host gene ITGBL1 [J]. Mol Ther, 2019, 27(2): 380-393.
[15] Chen X, Li X, Wu X, et al. Integrin beta-like 1 mediates fibroblast-cardiomyocyte crosstalk to promote cardiac fibrosis and hypertrophy [J]. Cardiovasc Res, 2023, 119(10): 1928-1941.
[16] Zhao J, Yang S, Xu Y, et al. Mechanical pressure-induced dedifferentiation of myofibroblasts inhibits scarring via SMYD3/ITGBL1 signaling [J]. Dev Cell, 2023, 58(13): 1139-1152.e6.
[17] Xu M Y, Qu Y, Li Z, et al. A 6 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis B [J]. Front Biosci (Landmark Ed), 2016, 21(3): 479-486.
[18] Wang M, Gong Q, Zhang J, et al. Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis [J]. Sci Rep, 2017, 7: 43446.
[19] Lee K C, Wu P S, Lin H C. Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis [J]. Clin Mol Hepatol, 2023, 29(1): 77-98.
[20] Wen J H, Li D Y, Liang S, et al. Macrophage autophagy in macrophage polarization, chronic inflammation and organ fibrosis [J]. Front Immunol, 2022, 13: 946832.