Survivin gene expression increases gastric cancer cell lymphatic metastasis by upregulating vascular endothelial growth factor-C expression levels

Zhang,Junyan; Zhu,Zhi; Sun,Zhe; Sun,Xuren; Wang,Zhenning; Xu,Huimian

doi:10.3892/mmr.2013.1858

Survivin gene expression increases gastric cancer cell lymphatic metastasis by upregulating vascular endothelial growth factor-C expression levels

Authors:
- Junyan Zhang
- Zhi Zhu
- Zhe Sun
- Xuren Sun
- Zhenning Wang
- Huimian Xu
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Affiliations: Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: December 11, 2013 https://doi.org/10.3892/mmr.2013.1858
Pages: 600-606

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Abstract

The aim of this study was to investigate the correlation between the expression of survivin and vascular endothelial growth factor‑C (VEGF‑C) in gastric cancer and the pathway by which survivin may affect gastric cancer lymphatic metastasis. The study may provide novel targets for treating gastric cancer lymphatic metastasis and distal dissemination. Survivin and VEGF‑C expression in gastric carcinoma and peri‑carcinoma (2 cm away from the carcinoma) tissues, obtained from 195 patients who underwent curative gastrectomy surgery (130 cases presented with lymph node metastasis and 65 cases presented without metastasis), was examined immunohistochemically using a tissue microarray. Plasmids containing survivin and VEGF‑C shRNA were constructed and transfected into SGC‑7901 gastric cancer cells. The expression levels of the two genes were examined using western blot analysis and qPCR, and the results were statistically analyzed. The expression levels of survivin and VEGF‑C were 51.3 and 55.4%, respectively, in gastric carcinoma. Survivin and VEGF‑C were located mainly in the cytoplasm of the tumor cells. The expression levels of survivin and VEGF‑C were significantly higher in patients with lymph node metastasis than in those without metastasis (P=0.008 and 0.001, respectively). Patients with high expression levels of survivin and VEGF‑C showed significantly less favorable survival rates compared with patients with low expression levels of those two genes (P=0.003 and 0.039, respectively). Moreover, patients with co‑expression of the two genes usually had a poorer prognosis (P=0.003). However, multivariate analysis demonstrated that neither of the two genes were an independent prognostic determinant. The levels of VEGF‑C expression may be regulated by survivin expression. Conversely, inhibiting VEGF‑C gene expression by shRNA did not reduce survivin expression at the mRNA or protein levels. Survivin and VEGF‑C were expressed in gastric cancer cells and were significantly associated with lymphatic metastasis. Survivin may be a regulator of VEGF‑C expression in gastric cancer cells, and is essential in invasion and lymphatic metastasis. Moreover, survivin may be able to serve as a chemotherapy target for gastric cancer.

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