Purpose: Overexpression of Axl  has been reported in many tumors, where it promotes tumorigenesis and progression, as well as correlates with the prognosis of different malignancies. However, Axl  expression and its function have rarely been reported in Wilms’ tumor (WT). This study aimed to reveal the clinical significance of Axl  expression in patients with WT and determine its mechanisms.
Materials and methods: We analyzed the expression of Axl  and its correlations with various clinicopathological features in 72 WT tissues and 72 adjacent non-cancerous tissues by immunohistochemistry. Cox proportional hazards regression models were used to investigate the correlations between Axl  expression and the prognosis of WT patients. Fresh frozen samples from 20 WT patients were examined using Western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). In WT cell line, after Axl  knockdown by sh-Axl  and growth arrest-specific 6 (Gas6) stimulation, the cell proliferation, migration and invasion abilities were detected by methyl-thiazolyl-tetrazolium (MTT), clone-forming, wound-healing and trans­well assays. Meanwhile, the tumor-forming ability was tested on nude mice xenograft models. Finally, the expression of several proteins in signal pathways was quantified by WB assays.
Results: Compared with the adjacent non-cancerous tissues, the expression of Axl  was significantly higher in WT tissues (P <0.05). High expression of Axl  was associated with tumor recurrence or lung metastasis of WT patients and was a prognostic factor for WT patients (P <0.05). In vitro assays, the proliferation, migration and invasion of WT cells decreased with Axl  knockdown and significantly increased with Axl  activation by Gas6 (P <0.05). In vivo assays, the ability of tumorigenicity in WT cells reduced dramatically after Axl  knockout (P <0.05). Moreover, PI3K–Akt  pathway proteins decreased with Axl  knockdown.
Conclusion: Our results suggest that Axl  is highly expressed in WT and is a prognostic factor, which could promote the progression of WT in vitro and in vivo. It may also be a potential biomarker for WT.
Keywords: Wilms’ tumor, Axl , prognosis, proliferation, invasion, migration