Downregulation of FOXK2 is associated with poor prognosis in patients with gastric cancer

Liu,Xi; Wei,Xiaodong; Niu,Wei; Wang,Dong; Wang,Bo; Zhuang,Hao

doi:10.3892/mmr.2018.9466

Downregulation of FOXK2 is associated with poor prognosis in patients with gastric cancer

Authors:
- Xi Liu
- Xiaodong Wei
- Wei Niu
- Dong Wang
- Bo Wang
- Hao Zhuang
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Affiliations: Department of Gastroenterology, Tianjin Nankai Hospital, Tianjin 300100, P.R. China, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300050, P.R. China, Department of Hepatic Biliary Pancreatic Surgery, Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450008, P.R. China
Published online on: September 7, 2018 https://doi.org/10.3892/mmr.2018.9466
Pages: 4356-4364
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Forkhead box (FOX)K2 (FOXK2) is a member of the FOX transcription factor family. It has been suggested previously that FOXK2 is required to suppress tumor growth; however, the exact role of FOXK2 in gastric cancer remains to be elucidated. In the present study, the association between FOXK2 expression and the clinicopathological characteristics of patients with gastric cancer was investigated. The prognostic value of FOXK2 expression and the significance of clinicopathological parameters in the overall survival (OS) and progression‑free survival of patients were also determined by survival analysis. To investigate the functional roles of FOXK2, it was downregulated in BGC‑823 cells using small interfering (si)RNA, and upregulated using a FOXK2 plasmid. Colony formation, Cell Counting Kit‑8 and cell proliferation analyses were conducted to examine the proliferation of gastric cancer cells. Transwell and wound‑healing assays were performed to investigate the effect of FOXK2 expression on gastric cancer cell migration and invasion. The clinical data demonstrated that FOXK2 expression was reduced in high‑grade gastric cancer tissues, and a low level of FOXK2 expression indicated a poor prognosis. The data obtained from the Human Protein Atlas revealed that patients with gastric cancer and a high level of FOXK2 expression had a longer OS time. The results of colony formation assays, Transwell and wound healing assays demonstrated that FOXK2 repressed the proliferation, invasion and migration of gastric cancer cells, respectively. The findings indicated that FOXK2 may serve as a promising therapeutic target in gastric cancer. Taken together, the findings of the present study demonstrated that FOXK2 functions as a tumor suppressor in gastric cancer; the loss of FOXK2 may induce the growth and invasion of gastric cancer cells.

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