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Monocarboxylate transporter 4 predicts poor prognosis in hepatocellular carcinoma and is associated with cell proliferation and migration

  • Original Article - Cancer Research
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Abstract

Purpose

Monocarboxylate transporter 4 (MCT4) is a critical component in the glycolytic metabolism of cancer cells, and is also important for malignant behavior. We investigated the expression profile of MCT4, its prognostic value in hepatocellular carcinoma (HCC) patients, its role in HCC cell proliferation and metastasis, and associated initial molecular mechanism.

Methods

MCT4 expression was examined through immunohistochemical staining of pathological specimens from 318 HCC patients who had undergone hepatectomy. The HCC cell lines were used to validate the relationship between MCT4 expression and cell proliferation, migration, and invasion.

Results

The results show that high MCT4 expression is indicative of elevated alpha fetoprotein levels and larger tumor size, which leads to poorer disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis shows that MCT4 expression is an independent prognostic factor for DFS and OS in HCC patients. In 91 recurrent HCC patients who underwent transarterial chemoembolization (TACE) treatment, low MCT4 expression predicted an effective treatment response and improved OS. Furthermore, in cell line experiments with MCT4 siRNA, cancer cell proliferation, migration, and invasion were closely correlated with the MCT4 expression. Knockdown of MCT4 was associated with down-regulation of phosphorylated AKT and HIF-1α.

Conclusions

MCT4 expression can predict survival and TACE treatment response for HCC patients. Furthermore, MCT4 plays an important role in HCC cell proliferation, migration, and invasion. The inhibition of MCT4 can induce inactivation of HIF-1α and inhibit phosphorylation of AKT. MCT4 may be a potential therapeutic target for the treatment of HCC.

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Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China

    Heng-Jun Gao, Yao-Jun Zhang, Dong-Sheng Zhou, Li Xu & Min-Shan Chen

  2. Department of Hepatobiliary Surgery and Liver Transplantation Center, Shandong Provincial Hospital Affiliated Shandong University, Jinan, 250021, China

    Ming-Chi Zhao, Guang-Bing Li & Jun Liu

Authors
  1. Heng-Jun Gao
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  2. Ming-Chi Zhao
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  3. Yao-Jun Zhang
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  4. Dong-Sheng Zhou
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  5. Li Xu
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  6. Guang-Bing Li
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  7. Min-Shan Chen
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  8. Jun Liu
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Corresponding author

Correspondence to Jun Liu.

Additional information

Heng-Jun Gao and Ming-Chi Zhao have contributed equally to this work.

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Gao, HJ., Zhao, MC., Zhang, YJ. et al. Monocarboxylate transporter 4 predicts poor prognosis in hepatocellular carcinoma and is associated with cell proliferation and migration. J Cancer Res Clin Oncol 141, 1151–1162 (2015). https://doi.org/10.1007/s00432-014-1888-8

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  • DOI: https://doi.org/10.1007/s00432-014-1888-8

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