Expressions And Clinical Significance Of CTHRC1Gene In Human Esophageal Squamous Cell Carcinoma

Objective: To compare the differences of the expressions of CTHRC1gene inesophageal squamous cell carcinoma(ESCC) tissues and their matched canceradjacent normal tissues, and to evaluate its possible correlation withclinicopathological parameters of the ESCC patients as well as their prognosis．Methods: Thirty specimens of esophageal squamous cell carcinoma and thirtyspecimens of their cancer adjacent normal tissues(≥5cm away from the tumor edge)were collected in our hospital between February2013and July2013. All of thepatients experienced radical surgery. SYBR Green Real-time quantitative PCR assaywas employed to analyze the expression of CTHRC1mRNA in esophageal squamouscell carcinoma(ESCC) tissues and their matched cancer adjacent normal tissues.99paraffin-embedded tissues of esophageal squamous cell carcinoma and theircorresponding adjacent normal tissues and their corresponding clinical data werecollected from January2005to December2007. The expression of CTHRC1proteinwas analyzed by immunohistochemical streptavidin-perosidase(S-P) method in ESCCtissues and corresponding adjacent normal tissues.The correlation between CTHRC1protein expression and clinicopathological features of ESCC was analyzed bychi-square analysis and Spearman correlation analysis．The cumulative survival ratewas analyzed by Kaplan-Meier method．The Cox’s proportional hazards regressionmodel was used to analyze the factors which influencing the patients’ prognosis.Results: In30specimens of esophageal squamous cell carcinoma and theirmatched cancer adjacent normal tissues，the results of Real-time quantitative PCRshowed that the expression level of CTHRC1mRNA in ESCC tissues was increasedsignificantly about5times than that of corresponding adjacent normal tissues，whichhas statistical significance（P<0.05）. In99paraffin-embedded tissue samples ofesophageal squamous cell carcinoma,CTHRC1protein expressed mainly in the cytoplasm and cell membrane of tumor cells. Immunohistochemical date showedthat the positive rate of CTHRC1protein expression in ESCC tissues wassignificantly higher than that of adjacent normal tissues（56.6%（56/99）vs5.1%（5/99），P <0.05）. In addition, the results of χ2test analysis showed that there wasa quite significant correlation between the high expression of CTHRC1protein andthe depth of tumor invasion、lymph node metastasis、TNM stage、and the survivalstatus of ESCC patients（χ2=6.991、12.278、7.020、10.631，all P <0.05），Butnot and gender、age、tumor location、tumor differentiation（χ2=0.451、2.567、4.304、0.382，all P>0.05）. Both of the Spearman correlation analysis results and the resultsof chi-square analysis were same. The results of Kaplan-Meier analysis showed thatthe5years survival rate of ESCC patients with a higher positive rate of CTHRC1expression had a poorer prognosis (χ2=9.251，P=0.002). The cumulative5yearssurvival rate of CTHRC1-positive patients was14.30%(8/56), whereas the survivalrate of CTHRC1-negative patients was44.20%（19/43）. The median survival timewas36months in patients of CTHRC1-positive, whereas that of the negativeexpression was54months. The Cox’s proportional hazards regression model analysisindicated that TNM stage (P=0.045) and CTHRC1expression (P=0.014) wereindependent predictors for ESCC patients.Conclusions： Both of the mRNA and protein levels of CTHRC1in humanesophageal squamous cell carcinoma are significantly up-regulated，and the survivalrate of CTHRC1-positive patients are lower. All the results implied that theexpression of CTHRC1gene may take part in the development、invasion、metastasisof the ESCC. and it may become one of the new molecular biomarkers to estimate theprognosis of ESCC patients．...