Significance Of The Expression Of Axin2,TGF-β1 And Smad4 In Colorectal Adenocarcinoma

Objective: This study observes the expression of Axin2, TGF-β1 andSmad4 in human colorectal adenocarcinoma, colorectal adenoma andcolorectal adjacent to adenocarcinoma, and then analyzes the relationshipbetween the expression and clinical pathological features, includinghistological type, differentiation, lymph node metastasis, tumor infiltrationdepth and Dukes’ stage, etc. The study analyzes the role of Axin2, TGF-β1 andSmad4 in EMT and plans to explore their potential functions in the occurrenceand development of colorectal cancer, and provide theoretical basis forexplaining the colorectal cancer. It’s also expected to evaluate the clinicalvalue of Axin2, TGF-β1 and Smad4 on diagnosis, treatment and prognosis ofcolorectal cancer.Methods: 150 cases of patients with colorectal adenocarcinoma and 50 cases with colorectal adenoma from Jan 2012 to Dec 2013 were collectedfrom Tangshan Gongren Hospital affiliated to Hebei Medical University. Thetissue microarray technology was used to make paraffin blocks whichcontained adenocarcinoma tissues, adenoma tissues and corresponding normalmucosa samples away from the tumor at least 2 cm. And the diagnosis wasconfirmed by pathologists in Tangshan Gongren Hospital. The SPimmunohistochemical technology was used to observe the expression ofAxin2, TGF-β1 and Smad4 protein in tissues, which including 140 cases ofadenocarcinoma tissues, 41 cases of adenoma tissues and 134 cases ofadjacent normal colorectal tissues while some tissues were lost during theprocess of immunohistochemistry.The measurement data were collected and enumeration data wereexpressed as a percentage. The association between expression level of targetfactors and clinical pathological features of colorectal adenocarcinoma wereanalyzed using SPSS13.0 statistical software by different statisticalmethods, including gender, age, differentiation, tumor infiltration depth,lymph node metastasis and pathological stage.Results: 1 The expression of Axin2 in the tissue of patients withcolorectal adenocarcinoma or adenoma: The expression level was different incolorectal adenocarcinoma tissue, colorectal adenoma tissue andpericarcinoma mucosa tissue. The positive expression rate of Axin2 incolorectal adenocarcinoma tissue is 53.57%(75/140), and in adenoma tissue itis 65.85%(27/41), and in normal tissue it is 95.52%(128/134). The differenceof expression rate is statistically significant(P<0.05). The expression of Axin2 in colorectal adenocarcinoma tissue is associated with lymph node metastasisand Dukes’ stages. The positive expression rate of Axin2 in colorectaladenocarcinoma with lymph node metastasis is 39.29%(22/56), and incolorectal adenocarcinoma with no lymph node metastasis it is 63.10%(53/84). The positive expression rate of Axin2 in colorectal adenocarcinoma ofDukes’ A and B is 66.10%(39/59), and in colorectal adenocarcinoma ofDukes’ C and D is 44.44%(36/81). The expression of Axin2 decreasedsignificantly in colorectal adenocarcinoma with lymph node metastasis and incancer of Dukes’ C and D stages. There is no correlation between theexpression and the gender, age, differentiation degree, pathological type andtumor infiltration depth.(P>0.05).2 The expression of TGF-β1 in the tissue of patients with colorectaladenocarcinoma or adenoma: The positive expression rate of TGF-β1 incolorectal adenocarcinoma tissue is 67.14%(94/140), and in adenoma tissue itis 36.59%(15/41), and in normal tissue it is 10.45%(14/134). The differenceof expression rate is statistically significant(P<0.05). The expression ofTGF-β1 in colorectal adenocarcinoma tissue is associated with tumorinfiltration depth and Dukes’ stages. The positive expression rate of TGF-β1 incolorectal adenocarcinoma localized in intestinal wall is 50.00%(30/60), andin colorectal adenocarcinoma invaded serosa is 80.00%(64/80). The positiveexpression rate of Axin2 in colorectal adenocarcinoma of Dukes’ A and B is35.59%(21/59), and in colorectal adenocarcinoma of Dukes’ C and D is90.12%(73/81). The positive expression rate of TGF-β1 in colorectaladenocarcinoma with lymph node metastasis is 82.14%(46/56), and incolorectal adenocarcinoma with no lymph node metastasis it is 57.14%(48/84). The difference of expression rate is statistically significant(P<0.05).There is no correlation between the expression and the gender, age,pathological type and differentiation degree(P>0.05).3 The expression of Smad4 in the tissue of patients with colorectaladenocarcinoma or adenoma: The expression level of Smad4 was different incolorectal adenocarcinoma tissue, colorectal adenoma tissue andpericarcinoma mucosa tissue. The positive expression rate of Smad4 incolorectal adenocarcinoma tissue is 48.57%(68/140), and in adenoma tissue itis 60.98%(25/41), and in normal tissue it is 92.54%(124/134). The differenceof expression rate is statistically significant(P<0.05). The expression ofSmad4 in colorectal adenocarcinoma tissue is associated with tumordifferentiation degree and lymph node metastasis. The positive expression rateof Smad4 in poorly differentiated colorectal adenocarcinoma with lymph nodemetastasis is 26.09%(6/23), and in Well and Moderately differentiatedcolorectal adenocarcinoma is 52.99%(62/117). The positive expression rate ofSmad4 in colorectal adenocarcinoma with lymph node metastasis is 33.93%(19/56), and in colorectal adenocarcinoma with no lymph node metastasis it is58.33%(49/84). The difference of expression rate is statistically significant(P<0.05). There is no correlation between the expression of Smad4 and thegender, age, tumor infiltration depth, pathological type and pathological Stage(P>0.05).4 Positive correlation between Axin2 and TGF-β1(X2=12.104,P=0.001),Axin2 and Smad4(X2= 15.394,P=0.000), TGF-β1 and Smad4(X2=34.619,P=0.000)were signifinant in colorectal carcinoma.Conclusions: 1 The expressions of Axin2 and Smad4 in colorectaladenocarcinoma tissue were significantly reduced than that in colorectaladenoma and non-carcinoma mucosa while the expressions of TGF-β1 incolorectal adenocarcinoma up-regulated. The down-regulated Axin2 andSmad4 and the up-regulated TGF-β1 might be involved in the process ofnormal mucosa-adenoma-adnocarcinoma.2 The down-regulated expressions of Axin2 and Smad4 and up-regulatedexpressions of TGF-β1 were related to the progress of colorectal cancerswhich might be atced as potential biomarkers for colorectal cancer.3 Axin2, TGF-β1 and Smad4 protein levels were relevant to each other,which indicated Axin2, TGF-β1 and Smad4 might play interact functions.