Expression Of FGFBP2 MRNA In Esophageal Squamous Cell Carcinoma And Its Functions

Objectives: Esophageal carcinoma is one of the most common digestive tract cancers in humans.It is a rapidly progressive disease with poor prognosis and the survival rate of patients after operation is lower.Therefore,searching for genes related to the development and prognosis of esophageal squamous cell carcinoma is an important objective.The aim of this study is to investigate the expression of human fibroblast growth factor binding protein 2(FGFBP2)mRNA in esophageal squamous cell carcinoma(ESCC)tissues and its function.Methods: The expression of FGFBP2 mRNA in 190 cases of ESCC and 42 cases of normal surgical margin tissues was detected by tissue microarray and RNAscope in situ hybridization.Observe the difference of expression of FGFBP2 mRNA in tumor tissues and normal tissues,and then analyze the correlation between the positive expression rate and postoperative survival time.The knockdown effect of FGFBP2 in ESCC cell lines were detected by Real-Time PCR;the effect of knockdown of FGFBP2 on invasion and migration of ESCC cell lines was analyzed by Transwell and Wound healing test in vitro;the effect of knockdown of FGFBP2 on proliferation of ESCC cell lines was detected by CCK-8 assay;and Western blot was used to detect the expression levels of protein related to proliferation,invasion and migration after knockdown FGFBP2 in esophageal squamous cell carcinoma cell line.Results:(1)The positive rate of mRNA expression of FGFBP2 in ESCC tissues was 25.8%,while in normal surgical margin tissues mRNA expression was all negative.FGFBP2 mRNA expression was significantly different between tumor and normal tissues(P < 0.0001).(2)Correlation analysis showed that the expression of FGFBP2 mRNA was not correlated with all of clinicopathological parameters.(3)Kaplan-Meier survival analysis showed that the survival time of the patients with positive expression was shorter than that of the patients with negative expression(P = 0.002),Cox regression analysis suggested FGFBP2 mRNA was an independent prognostic factor for ESCC patients(P = 0.023).(4)Knockdown of FGFBP2 significantly inhibited the invasion,migration and proliferation of ESCC cell lines KYSE150 and KYSE510(P = 0.001).(5)Knocking down FGFBP2 in esophageal squamous cell carcinoma cell lines KYSE150 and KYSE510,the protein expression level of E-cadherin increased and the level of phosphorylated AKT(p-AKT)decreased.Conclusions: The high expression of FGFBP2 mRNA in ESCC tissues was negatively correlated with survival time,suggesting that FGFBP2 mRNA may be an independent prognosis biomarker of ESCC.Functional studies revealed that FGFBP2 promotes proliferation of ESCC cells through activating the AKT pathway,and enhanced invasion and migration of ESCC cells through downregulating E-cadherin expression.