Han Li-Yan, Yang Jie-Ru, Zhao Ze-Hua, Gao Shuai, Fan Yu-Chen, Wang Kai
Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, PR China.
Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, PR China; Institute of Hepatology, Shandong University, Jinan 250012, PR China.
Pathol Res Pract. 2020 Oct;216(10):153147. doi: 10.1016/j.prp.2020.153147. Epub 2020 Jul 28.
HBV-associated hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and non-invasive early detection of HBV-associated HCC requires to be improved. To determine the alteration and clinical relevance of necroptosis and its key regulator receptor-interacting protein kinase 3 (RIPK3) in HBV-associated HCC, we detected the mRNA level of RIPK3 in peripheral blood mononuclear cells (PBMCs) and analyzed its correlation with clinical parameters. Here, we demonstrate that the expression of RIPK3 is elevated in patients with HBV-associated HCC compared to patients with chronic hepatitis B (CHB) and patients with HBV-related liver cirrhosis (LC). The mRNA level of RIPK3 is positively correlated with the severity of clinical manifestations and TNM stages. Moreover, the serum levels of RIPK3-asssocited cytokines are altered in consistent with the change of RIPK3 expression. The diagnostic accuracy of RIPK3 mRNA level is comparable to AFP test in discriminating HBV-associated HCC from LC and is better than AFP test in discriminating HBV-associated HCC from CHB. The combination of RIPK3 mRNA level and AFP test significantly improves the diagnosis of HBV-associated HCC. These data suggest that RIPK3 mRNA level is a biomarker in the onset and progression of HBV-associated HCC and may provide novel diagnostic strategies combined with the AFP test.
乙型肝炎病毒(HBV)相关的肝细胞癌(HCC)是全球癌症相关死亡的主要原因之一,HBV相关HCC的非侵入性早期检测仍有待改进。为了确定坏死性凋亡及其关键调节因子受体相互作用蛋白激酶3(RIPK3)在HBV相关HCC中的变化及其临床相关性,我们检测了外周血单个核细胞(PBMC)中RIPK3的mRNA水平,并分析其与临床参数的相关性。在此,我们证明,与慢性乙型肝炎(CHB)患者和HBV相关肝硬化(LC)患者相比,RIPK3在HBV相关HCC患者中的表达升高。RIPK3的mRNA水平与临床表现的严重程度和TNM分期呈正相关。此外,RIPK3相关细胞因子的血清水平随RIPK3表达的变化而发生相应改变。RIPK3 mRNA水平在区分HBV相关HCC与LC方面的诊断准确性与甲胎蛋白(AFP)检测相当,在区分HBV相关HCC与CHB方面优于AFP检测。RIPK3 mRNA水平与AFP检测相结合可显著提高HBV相关HCC的诊断率。这些数据表明,RIPK3 mRNA水平是HBV相关HCC发生和进展的生物标志物,可能与AFP检测相结合提供新的诊断策略。