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Metallothionein 1M suppresses tumorigenesis in hepatocellular carcinoma.

ABSTRACT: Members of the metallothionein (MT) family are involved in metal detoxifcation and in the protection of cells against certain electrophilic carcinogens. In present study, it was found that MT1M was downregulated in more than 77.1% (91/118) of hepatocellular carcinoma (HCC) tissues compared with adjacent non-tumor tissues. Furthermore, overexpression of MT1M inhibited cell viability, colony formation, cell migration and invasion in HCC cell lines and tumor cell growth in xenograft nude mice, and activated cell apoptosis in HCC cell lines. In addition, immunohistochemistry analysis showed MT1M was negative or weak staining in tumor tissues but moderate or strong staining in adjacent non-tumor tissues. The sensitivity and specificity of MT1M for HCC diagnosis were 76.27% and 89.83%, respectively. In conclusion, MT1M was identified as a potential tumor marker for HCC and may serve as a useful therapeutic agent for HCC gene therapy.

SUBMITTER: Fu CL

PROVIDER: S-EPMC5464848 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other

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Metallothionein 1M suppresses tumorigenesis in hepatocellular carcinoma.

Fu Cheng-Lin CL Pan Bing B Pan Ju-Hua JH Gan Mei-Fu MF

Oncotarget 20170501 20

Members of the metallothionein (MT) family are involved in metal detoxifcation and in the protection of cells against certain electrophilic carcinogens. In present study, it was found that MT1M was downregulated in more than 77.1% (91/118) of hepatocellular carcinoma (HCC) tissues compared with adjacent non-tumor tissues. Furthermore, overexpression of MT1M inhibited cell viability, colony formation, cell migration and invasion in HCC cell lines and tumor cell growth in xenograft nude mice, and ...[more]

PMID: 28380433

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Project description:BackgroundCopper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib.MethodsWe enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy.ResultsThe serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratio≥0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratio<0.999 (45.3 vs. 30.1 months, p<0.001). MT was significantly correlated with the Cu/Zn ratio and increased after the administration of lenvatinib. Using multivariate Cox regression analyses, it was determined that the Cu/Zn ratio (hazard ratio [HR]: 1.442, p = 0.008), alpha-fetoprotein (HR: 1.000, p<0.001) and BCLC stage (HR: 2.087, p<0.001) were independent predictors of survival.ConclusionsThe Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival.

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Metallothionein 1M suppresses tumorigenesis in hepatocellular carcinoma.

Publications

Metallothionein 1M suppresses tumorigenesis in hepatocellular carcinoma.

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