Ye Ziqi, Zhang Xin, Zhang Yanfang, Liu Linqing, Xuan Zixue, Huang Ping
Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Laboratory Medicine Center, Department of Pathology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Front Oncol. 2022 Feb 11;12:761021. doi: 10.3389/fonc.2022.761021. eCollection 2022.
Although the pathogenesis of hepatocellular carcinoma (HCC) is still unclear, hepatitis C virus (HCV) infection is considered a common cause of HCC. It has been reported that DDX60L can inhibit HCV replication, but its role in HCC is still poorly understood.
The expression levels of DDX60L in HCC tissues and in tissues adjacent to the tumor and their correlation with the clinicopathological features of patients were analyzed. We also used Kaplan-Meier curves of overall survival (OS) with Cox regression analysis and log-rank test to investigate the prognostic value of DDX60L in HCC. We further performed cell proliferation, Transwell, and wound healing assays to elucidate the role of DDX60L in HCC using the siRNA-DDX60L Hep3B or HCCLM3 cell line.
Univariate analysis showed that sex, Edmondson grade, microvascular invasion, tumor stage (III-IV/I-II), AFP, and DDX60L expression were strongly associated with the prognosis of HCC patients. The results of multivariate analysis further suggested that DDX60L might be an independent prognostic factor for OS in patients with HCC ( = 0.015, = 0.011). The low DDX60L expression in HCC patients with no-metastasis, age ≥55 years, tumor size <5 cm, Edmondson grade = I-II, microvascular invasion, no cirrhosis, HBV positivity, tumor stage = III-IV, AFP >20 μg/L, and multiple tumor was associated with poorer prognosis (0.05). Moreover, the expression of DDX60L was significantly lower in HCC samples (N = 285) than in the normal tissues adjacent to the tumor (N = 167, 0.001). There were no HCV-related HCC patients in this study. Additionally, we found that DDX60L knockdown can promote the proliferation of Hep3B cells, migration and invasion ability of Hep3B and HCCLM3 cells.
We found that the downregulation of DDX60L expression correlated with poor prognosis in patients with HCC, which may be independent of the HCV-related pathway. Furthermore, DDX60L significantly inhibited the proliferation of Hep3B cells, migration and invasion of Hep3B and HCCLM3 cells. Therefore, DDX60L can serve as a prognostic biomarker and therapeutic target for HCC.
尽管肝细胞癌（HCC）的发病机制仍不清楚，但丙型肝炎病毒（HCV）感染被认为是HCC的常见病因。据报道，DDX60L可抑制HCV复制，但其在HCC中的作用仍知之甚少。
分析DDX60L在HCC组织及其癌旁组织中的表达水平，以及它们与患者临床病理特征的相关性。我们还使用总生存（OS）的Kaplan-Meier曲线结合Cox回归分析和对数秩检验来研究DDX60L在HCC中的预后价值。我们进一步使用siRNA-DDX60L Hep3B或HCCLM3细胞系进行细胞增殖、Transwell和伤口愈合试验，以阐明DDX60L在HCC中的作用。
单因素分析显示，性别、Edmondson分级、微血管侵犯、肿瘤分期（III-IV/I-II）、甲胎蛋白（AFP）和DDX60L表达与HCC患者的预后密切相关。多因素分析结果进一步表明，DDX60L可能是HCC患者OS的独立预后因素（P = 0.015，HR = 0.011）。在无转移、年龄≥55岁、肿瘤大小<5 cm, Edmondson分级 = I-II、微血管侵犯、无肝硬化、乙肝病毒（HBV）阳性、肿瘤分期 = III-IV、AFP>20 μg/L和多灶性肿瘤的HCC患者中，DDX60L低表达与较差的预后相关（P<0.05）。此外，DDX60L在HCC样本（N = 285）中的表达明显低于癌旁正常组织（N = 167，P<0.001）。本研究中没有HCV相关的HCC患者。此外，我们发现敲低DDX60L可促进Hep3B细胞的增殖、Hep3B和HCCLM3细胞的迁移和侵袭能力。
我们发现DDX60L表达下调与HCC患者的不良预后相关，这可能独立于HCV相关途径。此外，DDX60L显著抑制Hep3B细胞的增殖、Hep3B和HCCLM3细胞的迁移和侵袭。因此，DDX60L可作为HCC的预后生物标志物和治疗靶点。
