| OBJECTIVE:To explore the the expression of EGFR, STAT3and p-STAT3in gastric cancer(GC) and its clinical significance.METHODS:The STAT3expression, Phosphorylated STAT3(p-STAT3) expression, and EGFR expression were evaluated by molecular detection methods of GC tissues, adjacent non-tumor tissues, GC cell lines, and normal gastric cell line. Cetuximab was administrated in each cell line for demonstration the correlations among above biomarkers. Survival analysis and relationship analysis were adopted for demonstrated the mechanism of EGFR/STAT3signaling Pathway contribution to progression of GC.RESULTS:1. The relative mRNA expression values of STAT3and EGFR in GC tissues were significantly much higher than those in adjacent non-tumor tissues (STAT3,3.40±0.62VS1.14±0.34, p<0.001; EGFR,2.87±1.58VS0.72±1.16, p<0.001). With100μg/mL cetuximab administration, the relative mRNA expression value of STAT3significantly decreased in SGC7901cell line (2.07VS1.02) and in MKN28cell line (1.75VS0.85), There was no any difference of relative mRNA expression value of STAT3in GES-1cell line regardless of cetuximab administration(0.63VS0.48).2. The relative protein expression values of STAT3, p-STAT3and EGFR in GC tissues were significantly much higher than those in adjacent non-tumor tissues (STAT3,1.99±0.32VS0.61±0.26,p=0.016; p-STAT3,1.34±0.41VS0.48±0.18, p=0.011; EGFR,2.49±0.62VS0.78±0.27,p=0.003), respectively.With100μg/mL cetuximab administration, the relative protein expression values of STAT3and p-STAT3significantly decreased in SGC7901(STAT3,2.35VS1.32; p-STAT3,1.80VS1.21) and MKN28cell lines (STAT3,2.18VS1.15; p-STAT3,1.76VS1.04), and decreased in MGC803cell line (STAT3,0.72VS0.45; p-STAT3,0.51VS0.24). However, there were no any differences of the relative protein expression values of STAT3and p-STAT3in GES-1cell line regardless of cetuximab administration (STAT3,0.42VS0.36; p-STAT3,0.22VS0.17)3.STAT3positive expression, p-STAT3positive expression, and EGFR positive expression were respectively detected in96(84.21%),89(78.07%), and75(65.79%) of114GC specimens, whereas31(27.19%),22(19.29%), whereas31(27.19%),22(19.29%), and33(28.95%) of114adjacent non-tumor tissue specimens,There were significantly statistical differences in the positive expression incidences of STAT3(p=0.017), p-STAT3(p=0.006), and EGFR (p=0.035) between GC and adjacent non-tumor tissue specimens, respectively.4. STAT3expression was significantly correlative with p-STAT3expression in GC tissues (p<0.001), STAT3expression was significantly correlative with EGFR expression in GC tissues (p=0.001), and p-STAT3expression was significantly correlative with EGFR expression in GC tissues (p=0.034).5.Univariate analysis showed a significant relationship between the overall survival (OS) and depth of tumor invasion, number of metastatic lymph nodes, size of tumor, location of tumor, ratio of metastatic lymph nodes (RML), extent of nodal metastasis, STAT3expression, p-STAT3expression, and EGFR expression, Furthermore, p-STAT3expression (hazard ratio (HR)=2.485;p=0.002), EGFR expression (HR=2.477;p<0.001), and ratio of metastatic lymph nodes (RML)(HR=1.543; p<0.001) were identified as the independent factors of OS in all enrolled GC Patients, following the multivariate analysis.6. The number of metastatic lymph nodes (HR=2.035;p=0.005) was identified as the independently relative factor of STAT3expression in GC tissues, the extent of nodal metastasis (HR=2.249;p=0.006) was identified as the independentlyrelative factor of p-STAT3expression in GC tissues, and ratio of metastatic lymph nodes (RML)(HR=1.595;p=0.009) and Lauren’s classification of tumor (HR=3.124;p=0.007) were identified as the independently relative factors of EGFR expression in GC tissues by using a multivariate logistic regression model analyses.CONCLUSION:The expression of EGFR, STAT3and p-STAT3in GC tissues were significantly much higher than those in adjacent non-tumor tissuees, and EGFR, STAT3and p-STAT3was associated with lymph node metastasis. |
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