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Original Research

High SPINK1 Expression Predicts Poor Prognosis and Promotes Cell Proliferation and Metastasis of Hepatocellular Carcinoma

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Abstract

Background

Serine protease inhibitor Kazal type I (SPINK1) is highly expressed and promotes tumor progress in different cancers. This study aimed to evaluate SPINK1’s prognostic value and its role in hepatocellular carcinoma (HCC) progress.

Methods

We use tissue micro-arrays containing 273 tumor and paired para-tumor tissues to evaluate SPINK1’s prognostic value in HCC. CCK8 cell proliferation assay, wound healing assays, transwell migration and invasion assays were performed to explore the effect of SPINIK1 on HCC cells. The Cancer Genome Atlas (TCGA) database and Gene set enrichment analysis (GSEA) were used to verify the prognosis value of SPINK1 in HCC and explore the underlying mechanisms.

Results

SPINK1 expression was significantly higher in tumor tissues than paired para-tumor tissues (P < 0.001). Higher SPINK1 expression in tumor was significantly associated with portal vein tumor thrombus formation (P = 0.019) and shorter overall survival (P = 0.029). SPINK1 expression in tumor tissue was an independent predictor for overall survival. SPINK1 increased proliferation (P < 0.001), enhanced migration and invasion ability of HCC cell lines (P < 0.001). GSEA revealed that glycine, serine, threonine and bile acid metabolism may be the underlying mechanism of SPINK1 in HCC.

Conclusions

In conclusion, high SPINK1 expression is associated with poor prognosis of HCC. SPINK1 promotes proliferation, migration and invasion ability of HCC cells.

This article is referred to by:
Current Perspective in the Management of Hepatocellular Carcinoma: Time to Get Personal!

Acknowledgements

The founders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This study was founded by the Natural Science Foundation of Guangdong Province (2014A030313108, 2015A030310061), Young Teacher Culture Project of Sun Yat-sen University (15ykpy15) and Medical Scientific Research Foundation of Guangdong Province (A2017229).

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