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Tumor Biology

, Volume 36, Issue 6, pp 4405–4415 | Cite as

Overexpression of NKX6.1 is closely associated with progressive features and predicts unfavorable prognosis in human primary hepatocellular carcinoma

  • Lin-Lin Huang
  • Yi Zhang
  • Jia-Xing Zhang
  • Long-Jun He
  • Ying-Rong Lai
  • Yi-Ji Liao
  • Xiao-Peng Tian
  • Hai-Xia Deng
  • Ying-Jie Liang
  • Hsiang-Fu Kung
  • Dan Xie
  • Sen-Lin Zhu
Research Article
  • 222 Downloads

Abstract

The homeobox gene NKX6.1 was recently identified in cervical tumors. This study was designed to explore the clinical and prognostic significance of NKX6.1 further in patients with primary hepatocellular carcinoma (HCC). The expression levels of NKX6.1 were examined using real-time PCR, Western blotting, and immunohistochemistry in HCC cell lines and HCC tissues. The invasion capability of cell lines following silencing or overexpression of NKX6.1 was investigated by Transwell assay. Cells proliferation was tested by MTT assays. Epithelial–mesenchymal transition (EMT) marker expression levels were detected in relation to NKX6.1 expression. Correlation between NKX6.1 immunohistochemical staining, clinicopathologic parameters, and follow-up data of HCC patients was analyzed statistically. NKX6.1 expression was higher in HCC tissues compared to the adjacent noncancerous tissue. NKX6.1 overexpression was significantly correlated with tumor size, tumor differentiation, clinical stage, metastasis, and relapse. Kaplan–Meier analysis revealed that NKX6.1 overexpression was related to unfavorable 5-year disease-free survival and overall survival. Importantly, multivariate analysis indicated that NKX6.1 overexpression was an independent unfavorable marker for overall survival. Moreover, a significant relationship was observed between NKX6.1 and EMT marker expression levels, and NKX6.1 knockdown inhibited cell invasion, and overexpression of NKX6.1 promotes cell proliferation in vitro. NKX6.1 is upregulated in HCC and is a reliable prognostic marker for patients with HCC.

Keywords

NKX6.1 Hepatocellular carcinoma Prognosis Epithelial–mesenchymal transition 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81072044 and 81172340) and the Natural Science Foundation of Guangdong (No. S2011010004653).

Conflicts of interest

None

Author contributions

S. L. Z. carried out the study. L. L. H., Y. Z., and J. X. Z. analyzed the data. L. L. H. wrote the paper. All authors read and approved the final manuscript.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Lin-Lin Huang
    • 1
  • Yi Zhang
    • 1
  • Jia-Xing Zhang
    • 2
  • Long-Jun He
    • 3
  • Ying-Rong Lai
    • 4
  • Yi-Ji Liao
    • 3
  • Xiao-Peng Tian
    • 3
  • Hai-Xia Deng
    • 3
  • Ying-Jie Liang
    • 4
  • Hsiang-Fu Kung
    • 3
    • 5
  • Dan Xie
    • 3
  • Sen-Lin Zhu
    • 1
  1. 1.Department of Gastroenterology and Hepatology, The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina
  2. 2.Department of Oncology, The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina
  3. 3.State Key Laboratory of Oncology in South China, Cancer CenterSun Yat-sen UniversityGuangzhouChina
  4. 4.Department of Pathology, The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina
  5. 5.State Key Laboratory of Oncology in South ChinaThe Chinese University of Hong KongHong KongChina

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