Combination of ULK1 and LC3B improve prognosis assessment of hepatocellular carcinoma
Combination of ULK1 and LC3B improve prognosis assessment of hepatocellular carcinoma
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ULK1和LC3B联合改善肝细胞癌的预后评估
DOI：
10.1016/j.biopha.2017.10.025
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发表时间：
2018-01-01
影响因子：
7.5
通讯作者：
Jia, Chang-Chang
中科院分区：
文献类型：
--
作者：
Wu, Dong-hao;Wang, Tian-Tian;Jia, Chang-Chang
背景：自噬在癌症中既有预防作用，也有促进作用，其作用可能在肿瘤发生过程中发生了变化。明确自噬在癌症中的动态作用可能会促进精确的诊断、治疗和指导药物设计。自噬相关蛋白ULK1是自噬的关键调节蛋白，其在肝细胞癌中的作用尚不清楚。本研究旨在研究ULK1的S能力和其他自噬标志物在预测肝癌预后中的作用，并探讨这些生物标志物在肝癌进展过程中自噬动态功能中的位置。方法：采用组织芯片免疫组织化学方法检测156例可手术切除的肝癌患者中ULK1和其他自噬标志物(LC3B)的表达。结果：ULK1的高表达和LC3B的高表达提示肿瘤体积较大(P=0.035)，血清甲胎蛋白水平较高(P=0.049)，淋巴结转移频率较高(P=0.015)，分期较晚(P=0.009)。生存分析显示，在肝癌患者中，ULK1的表达与PFS呈负相关(P=0.021)，而LC3B的表达与PFS呈负相关，但同时高表达的患者的5年总生存率(OS)较低(P=0.002)，5年无进展生存期(PFS)较短(P=0.003)。多因素分析显示，这两个联合指标是预测OS和PFS预后的独立因素。结论：ULK1是肝细胞癌患者的重要预后因素，联合应用可提高患者的预后评估水平。联合自噬生物标志物能更好地反映自噬的动态阶段，为如何干预肝细胞癌的自噬提供了潜在的治疗途径。
Background: Autophagy involves in both prevention and promotion in cancer, and its role probably changed during tumor development. Defined the dynamic function of autophagy in cancer may advance precision diagnostics, treatment, and guide drug design. Autophagy related protein ULK1 is key regulator of autophagy, and its role in hepatocellular carcinoma (HCC) was still unclear. This study aims to investigate ULK1's capacity along with other autophagic markers in predicting prognosis of HCC and explore position of these biomarkers in dynamic function of autophagy during HCC progression.Methods: The expression of ULK1 and other autophagic marker (LC3B) were test by Tissue microarray-based immunohistochemistry in 156 operable HCC patients. Survival analysis and correlation analysis were used to analysis influence of ULK1 and combined biomarker on clinical characteristics and prognosis.Results: The expression level of ULK1 was not related to all clinicopathological features, however, high expression of the ULK1 as well as LC3B overexpression suggested large tumor size (P = 0.035), high levels of serum AFP (P = 0.049), more frequency of node metastasis (P = 0.015), later TNM stage (P= 0.009). Survival analysis showed that ULK1 expression were negatively correlated with PFS rather than OS in HCC patients (P = 0.021), while LC3B were suggested to be negatively related with patients' PFS, However, Simultaneous high expression of ULK1 and LC3B had a poorer 5-year overall survival (OS) rate (P = 0.002) and shorter 5-year progression free survival (PFS)(P = 0.003), Further multivariate analysis revealed that the two combined biomarkers were independent factors to predict the prognosis of OS and PFS in all patients, while ULK1 alone or LC3B alone were only an independent predict factor for OS or PFS respectively.Conclusion: ULK1 were demonstrated to be an important prognostic factor for HCC patient, and it combined LC3B would improve prognosis assessment of the patients. Combined autophagic biomarkers would better represent dynamic stage of autophagy and It might provide a potential therapeutic way that how to interfere autophagy in HCC.