Zhan Yating, Tao Qiqi, Lang Zhichao, Lin Lifan, Li Xinmiao, Yu Suhui, Yu Zhengping, Zhou Guangyao, Wu Kaifeng, Zhou Zhenxu, Yu Zhixian, Zheng Jianjian
Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
J Med Virol. 2023 Oct;95(10):e29157. doi: 10.1002/jmv.29157.
It is known that ribonucleotide reductase M2 (RRM2) could be induced by hepatitis B virus (HBV) via DNA damage response. However, whether RRM2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B (CHB) patients is still unclear. In this study, CHB patients from GSE84044 (a transcriptome data from GEO data set) were downloaded and RRM2 was selected as a hub gene. Interestingly, a positive correlation was found between serum RRM2 and liver fibrosis stage. The similar results were found in CHB patients with normal alanine aminotransferase (ALT). Notably, RRM2 could effectively differentiate preliminary fibrosis from advanced fibrosis in CHB patients with/without normal ALT. In addition, RRM2 had a better performance in diagnosing liver fibrosis than two commonly used noninvasive methods (aspartate aminotransferase-to-platelet ratio index and fibrosis index based on the four factors), two classic fibrotic biomarkers (hyaluronic acid and type IV collagen) as well as Mac-2 binding protein glycosylation isomer, a known serum fibrosis marker. Moreover, CHB patients with high RRM2, who were associated with advanced fibrosis, had higher expressions of immune checkpoints. Overall, serum RRM2 may be a promising biomarker for diagnosing and monitoring liver fibrosis in CHB patients.
已知核糖核苷酸还原酶 M2(RRM2)可通过 DNA 损伤反应被乙型肝炎病毒(HBV)诱导。然而,RRM2 是否是慢性乙型肝炎(CHB)患者诊断和监测肝纤维化的潜在生物标志物仍不清楚。在这项研究中,从 GSE84044(来自 GEO 数据集的转录组数据)中下载了 CHB 患者的数据,并选择了 RRM2 作为枢纽基因。有趣的是,血清 RRM2 与肝纤维化分期呈正相关。在 ALT 正常的 CHB 患者中也发现了类似的结果。值得注意的是,RRM2 可有效区分 CHB 患者 ALT 正常和异常时的早期纤维化和晚期纤维化。此外,RRM2 在诊断肝纤维化方面的表现优于两种常用的非侵入性方法(天冬氨酸转氨酶-血小板比值指数和基于四个因素的纤维化指数)、两种经典的纤维化生物标志物(透明质酸和 IV 型胶原)以及 Mac-2 结合蛋白糖基化异构体,一种已知的血清纤维化标志物。此外,与晚期纤维化相关的高 RRM2 的 CHB 患者,其免疫检查点表达水平更高。总体而言,血清 RRM2 可能是 CHB 患者诊断和监测肝纤维化的有前途的生物标志物。