TY - JOUR
T1 - Loss of Tid1/Dnaja3 co-chaperone promotes progression and recurrence of hepatocellular carcinoma after surgical resection
T2 - A novel model to stratify risk of recurrence
AU - Chen, Kuan Yang
AU - Huang, Yi Hsiang
AU - Teo, Wan Huai
AU - Chang, Ching Wen
AU - Chen, Yu Syuan
AU - Yeh, Yi Chen
AU - Lee, Chieh Ju
AU - Lo, Jeng Fan
N1 - Funding Information:
Funding: This research was funded by research grant from Department of Health, Taipei City Government (Grant No.10501-62-034, 10601-62-038, 10701-62-026), National Yang-Ming University (108CRC-T402), and the Ministry of Science and Technology, Taiwan (MOST 105-2320-B-010 -025 -MY3, MOST 106-2911-I-010 -513, MOST 107-2314-B-010-024-MY3, MOST 108-2811-B-010-534, and MOST 108-2314-B-010-009-MY3).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - Biomarker and recurrence
KW - HBV
KW - Hepatocellular carcinoma
KW - Nrf2
KW - Tid1
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U2 - 10.3390/cancers13010138
DO - 10.3390/cancers13010138
M3 - Article
AN - SCOPUS:85099763898
SN - 2072-6694
VL - 13
SP - 1
EP - 15
JO - Cancers
JF - Cancers
IS - 1
M1 - 138
ER -