| Objectives:To investigate and analyze the relationship between the expression of FGFR and the pathological features of patients with OSCC and to assess whether FGFR1,FGFR2,FGFR3 and FGFR4 can be considered as prognostic biomarkers and potential therapeutic targets in OSCC.Materials and Methods: 1 Total protein was extracted from 10 OSCC cell lines and the expression of FGFRs was detected by Western blot.The localization of FGFRs was further demonstrated by immunofluorescence staining in SCC25 and HN6 cell lines.2 Immunohistochemistry was used to detect FGFRs expression in oral squamous carcinoma tissues and corresponding normal tissue samples.3 Investigate the expression of FGFRs in OSCC cancer patients and examine its relationship with clinicopathological features and prognosis in OSCC.4 CCK8 and colony-forming unit assays were used to evaluate the effect of AZD4547,a selective FGFR inhibitor,on proliferation of OSCC cells.Results: 1 FGFR1 expression was detected in six of ten cell lines and FGFR2,3 and 4 was detectable in all the cell lines.The expression of FGFR1,2 and 4 was mainly in the nucleus and cytoplasm while FGFR3 was predominantly localized in cytoplasm.2 The expression of FGFRs was higher in carcinoma tissues than in corresponding normal mucosa tissue(FGFR1,P<0.001;FGFR2,P<0.001;FGFR3,P<0.01;FGFR4,P<0.001).3 In patients with OSCC,according to the patients' baseline characteristics,there was no significant difference between the expression of FGFR1,FGFR2,FGFR3 and FGFR4 and sex,age and recurrence.Lymph node metastasis was significantly correlated with the expression of FGFR2,FGFR3 and FGFR4(FGFR2,P=0.009;FGFR3,P=0.022,FGFR4,P=0.012).With the development f TNM stages,the expression of FGFR3 and FGFR4 increased significantly(FGFR3,P=0.026;FGFR4,P=0.003).The patients with moderately or poorly athological differentiation grade had higher FGFR1,FGFR3,FGFR4 expression n cancerous tissues than those with well differentiated tumors(FGFR1,p=0.02;FGFR3,P=0.013;FGFR4,P=0.02).The expression of FGFR2 was ignificantly correlated with drinking status(P=0.002).High expression of FGFR1,FGFR2,FGFR3 or FGFR4 were significantly ssociated with poor overall survival(P<0.0001,P=0.023,P<0.0001,P=0.0007,respectively)on univariate analysis in 110 patients with OSCC.Multivariate Cox odel analysis showed that lymph node metastasis(HR,2.648;95%CI,1.019-5.980;P=0.045),FGFR1(HR,2.450;95%CI,1.202-4.994;P=0.014)and GFR4(HR,3.075;95%CI,1.332-7.098;P=0.009)were independent rognostic factors in OSCC.Co?overexpression of three or four FGFR members n the primary tumors was found to be significantly associated with a poorer 5-years survival compared to the expression of none,only one or two of these roteins(P<0.0001).The 5-years survival was 21.4,34.6,73.3,81.0 and 94.7% in patients exhibiting high expression of all four,three,two,one and none of these FGFRs,respectively.4 AZD4547 inhibited the proliferation of OSCC cells in a concentration dependent anner.AZD4547 inhibited the phosphorylation levels of FGFR1,ERK and AKT.Conclusions: 1 FGFR co-expressed in OSCC cell lines and the expression of FGFR1,2,4 was mainly in the nucleus and cytoplasm while FGFR3 was predominantly localized in cytoplasm.2 Higher expression of FGFR1,FGFR2,FGFR3 and FGFR4 was observed in the tumor tissue compared to the normal mucosa tissue.3 Lymph node metastasis was significantly correlated with the expression of FGFR2,FGFR3 and FGFR4.FGFR1,FGFR3 and FGFR4 were higher in patients with moderately or poorly pathological differentiation grade than those with well differentiated tumors.High expression of FGFR1 or FGFR4 was associated with tumor progression and poor survival in patients with OSCC.FGFR1 and FGFR4 may be considered as independent prognostic factors in OSCC.Co?overexpression of three or four FGFR members in the primary tumors was a poorer prognostic marker for patients with OSCC.4 AZD4547 can inhibit OSCC cell proliferation and the phosphorylation levels of FGFR1,ERK and AKT,which implied that FGFR1 maybe a potential molecular for target therapy in OSCC. |
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