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IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-01-27 DOI:10.1016/j.xcrm.2025.101935

Hong Yang, Dila Atak, Meng Yuan, Mengzhen Li, Ozlem Altay, Elif Demirtas, Ibrahim Batuhan Peltek, Burge Ulukan, Buket Yigit, Tarik Sipahioglu, María Bueno Álvez, Lingqi Meng, Bayram Yüksel, Hasan Turkez, Hale Kirimlioglu, Burcu Saka, Cihan Yurdaydin, Murat Akyildiz, Murat Dayangac, Mathias Uhlen, Jan Boren, Cheng Zhang, Adil Mardinoglu, Mujdat Zeybel

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引用次数: 0

摘要

各种原因引起的慢性肝损伤和炎症可导致肝纤维化和肝硬化，并有可能诱发肝细胞癌。肝纤维化及其进展的分子机制仍不完全清楚。利用蛋白质转录组学方法，我们分析了 330 人的肝脏和血浆样本，其中包括 40 名健康人和 290 名因慢性病毒感染、饮酒或代谢功能障碍相关性脂肪肝而出现组织学特征性纤维化的患者。我们的研究结果揭示了晚期肝纤维化中与细胞外基质、免疫反应、炎症和新陈代谢相关的失调通路。我们还发现了132种与晚期肝纤维化相关的循环蛋白，与纤维化-4模型（AUROC 0.85 [95% CI 0.78-0.93]）相比，神经筋膜蛋白和生长分化因子15对晚期肝纤维化的预测性能更优（接收者操作特征曲线下面积 [AUROC] 0.89 [95% 置信区间 (CI) 0.81-0.97]）。这些发现深入揭示了纤维化的发病机制，并凸显了更准确的无创诊断的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Integrative proteo-transcriptomic characterization of advanced fibrosis in chronic liver disease across etiologies.

Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease. Our findings reveal dysregulated pathways related to extracellular matrix, immune response, inflammation, and metabolism in advanced fibrosis. We also identify 132 circulating proteins associated with advanced fibrosis, with neurofascin and growth differentiation factor 15 demonstrating superior predictive performance for advanced fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared to the fibrosis-4 model (AUROC 0.85 [95% CI 0.78-0.93]). These findings provide insights into fibrosis pathogenesis and highlight the potential for more accurate non-invasive diagnosis.

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.