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Expression and prognostic significance of epithelial tissue-specific transcription factor ESE3 in hepatocellular carcinoma

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Abstract

Background

Epithelium-specific ETS 3 (ESE3) is down-regulated frequently in several malignancies and involved in carcinogenesis and progression. However, ESE3 expression pattern and its relationship with clinical features and prognosis in hepatocellular carcinoma (HCC) are still largely unknown.

Methods

ESE3 expression was analyzed by quantitative real-time PCR and western blotting in HCC cell lines, and then, it was analyzed by immunohistochemistry in HCC tissues and peritumoral normal tissues from total 94 HCC patients. The relationship between ESE3 expression and clinical features was investigated to illustrate the potential prognostic value in HCC. ESE3 roles on HCC progression were evaluated in vitro and vivo by MTT assay and mice tumor model, respectively.

Results

ESE3, mainly located in the cytoplasm, was remarkably down-regulated in HCC tissues and cell lines. Low ESE3 expression was positively associated with tumor progression and metastasis features. Kaplan–Meier analysis demonstrated that low ESE3 expression contributed to poor recurrence-free survival (RFS) and overall survival (OS) (both p < 0.01) of patients, and maintained its prognostic value in predicting poor RFS and OS of “Early-stage” HCC patients regardless of clinical features being studied. Multivariate survival analysis was also identified ESE3 as an independent prognostic factor for RFS (p = 0.05 for marginal significance) and OS (p = 0.031). ESE3 expression restoration in cells led to a significant inhibition in HepG2 cell proliferation in vitro and vivo (both p < 0.001).

Conclusions

Down-regulated ESE3 expression in HCC tissues could serve as a potential therapeutic target against HCC and appears to be as a poor prognostic indicator for prognosis, especially in “Early-stage” HCC patients.

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Acknowledgements

We are grateful to Prof. Bo Zhang (Shanghai Harmonious One Biotech Co., Ltd, Shanghai, China) for kindly providing HCC cell lines, technical assistance, and helpful discussion regarding this research area. This study was funded by grants from National Natural Science Foundation of China (No. 81602550 and No. 81871700), Science and Technology Development Project of Shandong Province (No. 2018GSF118072), and Natural Science Foundation of Shandong Province (No. ZR2018BH003).

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Authors and Affiliations

  1. Department of Infectious Diseases, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China

    Zhuozhen Lyu, Mingze Ma, Yuhua Zhu, WanHua Ren & Tao Li

  2. Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China

    Yantian Xu

  3. Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China

    Xinxing Wang

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  1. Zhuozhen Lyu
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  2. Mingze Ma
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  5. Yuhua Zhu
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Correspondence to WanHua Ren or Tao Li.

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The authors declare no conflict of interest.

Research involving human participants and animal

Ethical approval for using human samples and animals was obtained from the Ethics Committee of Provincial Hospital affiliated to Shandong University.

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Patients had to give written informed consent for the use of their tumor tissues for further investigations at time of the initial diagnosis.

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Lyu, Z., Ma, M., Xu, Y. et al. Expression and prognostic significance of epithelial tissue-specific transcription factor ESE3 in hepatocellular carcinoma. Int J Clin Oncol 25, 1334–1345 (2020). https://doi.org/10.1007/s10147-020-01675-0

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  • DOI: https://doi.org/10.1007/s10147-020-01675-0

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