Abstract:

Objective To detect the expression differences of Wnt signaling pathway related molecules β-catenin, Cyclin D1 and Dickkopf-1 (DKK1) in breast disease tissues, and to explore their application value in pathologically aided diagnosis of breast cancer. Methods From January 2008 to August 2019, 90 cases of breast tissue specimens in the Cancer Center of Guangzhou Medical University were collected, including 30 cases of breast hyperplasia, 30 cases of breast intraductal carcinoma and 30 cases of breast invasive ductal carcinoma. The expressions of β-catenin, Cyclin D1 and DKK1 in breast tissue of each group were detected by immunohistochemistry. Oncomine database and KM plotter database were used to analyze the expression differences of β-catenin, Cyclin D1 and DKK1 in breast cancer and normal breast tissues and their relationships with survival prognosis of patients with breast cancer, and to verify the results of immunohistochemistry. Receiver operating characteristic (ROC) curve was used to evaluate the efficacies of each molecule in pathologically aided diagnosis. Results There were statistically significant differences in β-catenin, Cyclin D1 and DKK1 expressions among breast hyperplasia, breast intraductal carcinoma and breast invasive ductal carcinoma (χ²=7.766, P=0.021; χ²=24.133, P<0.001;χ²=11.585, P=0.003). The expression of β-catenin in breast invasive ductal carcinoma group was significantly higher than that in breast intraductal carcinoma group and breast hyperplasia group (Z=-2.367, P=0.018; Z=-2.462, P=0.014). The expression of Cyclin D1 in breast invasive ductal carcinoma group and breast intraductal carcinoma group was significantly higher than that in breast hyperplasia group (Z=-4.166, P<0.001;Z=-4.174, P<0.001). The expression of DKK1 in breast invasive ductal carcinoma group and breast intraductal carcinoma group was significantly higher than that in breast hyperplasia group (Z=-3.090, P=0.002; Z=-2.923, P=0.003). The results of bioinformatics analysis showed that compared with normal breast tissue, the expression of β-catenin mRNA in invasive breast cancer tissue increased by 2.33 times (t=15.242, P<0.001), the expression of Cyclin D1 mRNA in breast intraductal carcinoma tissue increased by 6.64 times (t=7.152, P=0.006), while the expression of DKK1 mRNA in normal breat tissue was 3.41 times higher than that in invasive breast cancer tissue, with no statistically significant difference (t=-13.193, P>0.999). The median survival time of breast cancer patients in Cyclin D1 high expression group was 173.2 months, which was shorter than 228.9 months in low expression group (P<0.001). The upper quartile survival time of breast cancer patients in DKK1 high expression group was 55.1 months, which was longer than 40.4 months in low expression group (P<0.001). The breast invasive ductal carcinoma and breast intraductal carcinoma were combined into tumor group, the sum of the immunohistochemistry scores of β-catenin and Cyclin D1 minus the immunohistochemistry score of DKK1 was used as the combined scoring scheme 1, and the sum of β-catenin and Cyclin D1 immunohistochemistry score was used as the combined scoring scheme 2. ROC curve analysis showed that the area under the curve (AUC) of β-catenin, Cyclin D1, combined scoring scheme 1 and combined scoring scheme 2 for pathologically aided diagnosis of breast cancer were 0.65 (P=0.080), 0.81 (P<0.001), 0.70 (P=0.023) and 0.78 (P=0.001), respectively. The AUC of Cyclin D1 and combined scoring scheme 2 were ≥0.7, which had good value in pathologically aided diagnosis. Conclusion Wnt signaling pathway related molecules Cyclin D1 and Cyclin D1 combined with β-catenin detection has a good value in the pathologically aided diagnosis of breast cancer.

Key words: Breast neoplasms, Beta catenin, Cyclin D1, Dickkopf-1