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Properties and Clinical Relevance of Speckle-Type POZ Protein in Human Colorectal Cancer

  • Original Article
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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

The aims of this study are to evaluate the effect of Speckle-type POZ protein (SPOP) in colorectal cancer (CRC) patients and explore its significance in the prognosis.

Methods

We used immunohistochemistry to detect the expression of SPOP in CRC. Moreover, this result was further confirmed at the protein and messenger RNA (mRNA) level in paired CRC specimens and matched adjacent noncancerous colon tissues by Western blotting and real-time quantitative PCR (qRT-PCR), respectively. Furthermore, we evaluate the effects of SPOP on CRC cell proliferation and migration in vitro. The Kaplan–Meier method and log-rank test were employed to compare the overall survival between SPOP low expression group and SPOP high expression group. Correlation of survival with clinicopathologic parameters, including SPOP level, was investigated with multivariate analyses.

Results

We confirmed frequent SPOP downregulation in both mRNA (P = 0.0286) and protein (P = 0.004) levels in CRC tissues as compared to matched adjacent nontumorous tissues. Besides, the downregulated SPOP expression in CRC tissues was significantly correlated to poor differentiation (P = 0.013), distant metastasis (P = 0.003), gross type (P < 0.001), and high TNM stage (P = 0.002). Kaplan–Meier survival analysis showed that low SPOP expression exhibited a significant correlation with poor prognosis for CRC patients. Overexpression of SPOP in CRC cell lines significantly suppressed cell proliferation, migration, and clone formation. In contrast, SPOP knockdown dramatically promoted cell proliferation, migration, and clone formation in vitro. In addition, overexpression of SPOP increased E-cadherin and suppressed vimentin in HCT116 cells and silencing of SPOP reversed all these biomarkers. Furthermore, SPOP significantly downregulated MMP2 and MMP7 protein levels in HCT116 cell lines.

Conclusion

Our results suggest that SPOP plays a pivotal role in colorectal cancer (CRC) through mesenchymal–epithelial transition and MMPs, and it may be a potential therapeutic target in colorectal cancer.

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Acknowledgments

This work is supported by the grants from the China Postdoctoral Science Foundation and the Department of Health of Jiangsu Province of China (no. H201214).

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    Authors and Affiliations

    1. Department of General Surgery, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu Province, People’s Republic of China

      Junfei Xu, Feiran Wang, Yasu Jiang, Jinpeng Chen & Jun Qin

    2. Medical College of Nantong University, Nantong, 226001, Jiangsu Province, People’s Republic of China

      Haiyan Jiang

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    1. Junfei Xu
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    2. Feiran Wang
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    3. Haiyan Jiang
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    4. Yasu Jiang
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    Correspondence to Jinpeng Chen or Jun Qin.

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    Junfei Xu and Feiran Wang contributed equally to this work.

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    Xu, J., Wang, F., Jiang, H. et al. Properties and Clinical Relevance of Speckle-Type POZ Protein in Human Colorectal Cancer. J Gastrointest Surg 19, 1484–1496 (2015). https://doi.org/10.1007/s11605-015-2767-6

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