Gastric cancer (GC) is one of the most common cancers, and the second most common cause of cancer deaths worldwide. Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family and its upregulation is closely correlated with tumor progression and prognosis of multiple cancer types, including GC. FOXQ1 has been shown to regulate EMT and function in human cancers. However, the role of FOXQ1 in regulating EMT in GC and the exactly mechanism has not been clarified. The purpose of this study was to investigate the effects of FOXQ1 on EMT in human GC. FOXQ1 protein was detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. We examined the cell biology and molecular biology changes after overexpression and knockdown of FOXQ1 in gastric cancer cells in vitro. To further understand the underlying mechanisms of EMT promoted by FOXQ1, we examined the changes of target genes of FOXQ1 after overexpression and knockdown of FOXQ1 in gastric cancer cells. In the present study, we demonstrate that FOXQ1 is overexpressed in GC tissues and its expression level is closely correlated with histologic differentiation, pTNM stage, and lymphatic metastasis of GC. Kaplan-Meier survival analysis showed that a high expression level of FOXQ1 resulted in a significantly poor prognosis of GC patients. FOXQ1 modulated GC cell invasion in vitro, and induced E-cadherin repression. FOXQ1 also upregulated the expression of vimentin in vitro. The Snail signaling pathway was likely involved in the induction of EMT by FOXQ1 in GC. Our results demonstrate that FOXQ1 is a prognostic marker for patients with GC, FOXQ1 over-expression is involved in acquisition of the mesenchymal phenotype of gastric cancer cells, and that subsequent Snail expression is essential for induction of EMT. The results suggest that FOXQ1 is a potential therapeutic target for the development of therapies for GC.
BackgroundForkhead box Q1 (FOXQ1, also known as HFH1), a member of the forkhead transcription factor family, has been demonstrated to be overexpressed in multiple tumors and is thought to be an indicator of poor clinical outcomes.MethodsA meta-analysis using qualified relevant literature was performed to evaluate the prognostic significance of FOXQ1 in various malignant solid tumors. A search of electronic databases was conducted in MEDLINE, Embase, and the Cochrane Library to identify relevant studies published from 1966 to July 30, 2016, and the studies were identified by further evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for analyses were assessed to investigate the association between FOXQ1 expression and overall survival (OS) of patients with malignant solid tumors.ResultsA total of 1,520 patients from six studies (seven cohorts) with multiple malignant solid tumors were included. For OS, high FOXQ1 expression could significantly predict worse outcome with the pooled HR of 1.38 (95% CI: 1.17–1.59; P<0.001). The subgroup analysis suggested that the elevated levels of FOXQ1 appear to be associated with worse OS in hepatocellular carcinoma (HR =1.34; 95% CI: 1.11–1.57; P<0.001) and other cancers (HR =1.62; 95% CI: 1.09–2.14; P<0.001).ConclusionThis meta-analysis indicated that the high expression of FOXQ1 is associated with an adverse OS in malignant solid tumors, suggesting that FOXQ1 may be a predictor of poor prognosis for the development of malignant solid tumors.
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