Chen Kuan-Yang, Huang Yi-Hsiang, Teo Wan-Huai, Chang Ching-Wen, Chen Yu-Syuan, Yeh Yi-Chen, Lee Chieh-Ju, Lo Jeng-Fan
Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Institute of Neuroscience, National Chengchi University, Taipei 11605, Taiwan.
Cancers (Basel). 2021 Jan 4;13(1):138. doi: 10.3390/cancers13010138.
Tid1, a mitochondrial co-chaperone protein, acts as a tumor suppressor in various cancer types. However, the role of Tid1 in hepatocellular carcinoma (HCC) remains unclear. First, we found that a low endogenous Tid1 protein level was observed in poorly differentiated HCC cell lines. Further, upregulation/downregulation of Tid1 abrogated/promoted the malignancy of human HCC cell lines, respectively. Interestingly, Tid1 negatively modulated the protein level of Nrf2. Tissue assays from 210 surgically resected HCC patients were examined by immunohistochemistry (IHC) analyses. The protein levels of Tid1 in the normal and tumor part of liver tissues were correlated with the clinical outcome of the 210 HCC cases. In multivariate analysis, we discovered that tumor size > 5 cm, multiple tumors, presence of vascular invasion, low Tid1 expression in the non-tumor part, and high Nrf2 expression in the non-tumor part were significant factors associated with worse recurrence-free survival (RFS). A scoring system by integrating the five clinical and pathological factors predicts the RFS among HCC patients after surgical resection. Together, Tid1, serving as a tumor suppressor, has a prognostic role for surgically resected HCC to predict RFS.
Tid1是一种线粒体辅助伴侣蛋白，在多种癌症类型中发挥肿瘤抑制作用。然而，Tid1在肝细胞癌（HCC）中的作用仍不清楚。首先，我们发现在低分化HCC细胞系中观察到内源性Tid1蛋白水平较低。此外，Tid1的上调/下调分别消除/促进了人HCC细胞系的恶性程度。有趣的是，Tid1负向调节Nrf2的蛋白水平。通过免疫组织化学（IHC）分析对210例手术切除的HCC患者进行组织检测。肝组织正常和肿瘤部分的Tid1蛋白水平与210例HCC病例的临床结果相关。在多变量分析中，我们发现肿瘤大小>5 cm、多发肿瘤、存在血管侵犯、非肿瘤部分Tid1低表达以及非肿瘤部分Nrf2高表达是与无复发生存期（RFS）较差相关的显著因素。通过整合这五个临床和病理因素的评分系统可预测手术切除后HCC患者的RFS。总之，Tid1作为一种肿瘤抑制因子，对手术切除的HCC预测RFS具有预后作用。
