Ｒｅｌａｔｉｏｎｓｈｉｐ ｂｅｔｗｅｅｎ ｅｘｐｒｅｓｓｉｏｎ ｏｆ ＵＥＶ１Ａ， ＵＢＥ２Ｎ ａｎｄ ｅｐｉｔｈｅｌｉａｌ ｍｅｓｅｎｃｈｙｍａｌ ｔｒａｎｓｆｏｒｍａｔｉｏｎ ｉｎ ｂｒｅａｓｔ ｃａｎｃｅｒ ａｎｄ
ｉｔｓ ｃｌｉｎｉｃａｌ ｐｒｏｇｎｏｓｔｉｃ ｖａｌｕｅ Ｗｕ Ｘｉｎｙａｎ， Ｌｉｎ Ｘｉａｏｌｏｎｇ， Ｗａｎｇ Ｊｉａｎｂａｏ， Ｈｕａｎｇ Ｘｉｎｙｕ， Ｔａｎｇ Ｒｅｎｍｅｉ． Ｄｅｐａｒｔｍｅｎｔ ｏｆ Ｂｒｅａｓｔ
ａｎｄ Ｔｈｙｒｏｉｄ Ｓｕｒｇｅｒｙ， Ｑｉｏｎｇｈａｉ Ｐｅｏｐｌｅ ＇ｓ Ｈｏｓｐｉｔａｌ ／ Ｈａｉｎａｎ Ｅａｓｔｅｒｎ Ｒｅｇｉｏｎａｌ Ｍｅｄｉｃａｌ Ｃｅｎｔｅｒ， Ｈａｉｎａｎ Ｐｒｏｖｉｎｃｅ， Ｑｉｏｎｇｈａｉ
５７１４００， Ｃｈｉｎａ
Ｃｏｒｒｅｓｐｏｎｄｉｎｇ ａｕｔｈｏｒ： Ｗａｎｇ Ｊｉａｎｂａｏ， Ｅ⁃ｍａｉｌ： ４０６２４３６４０＠ ｑｑ． ｃｏｍ

Ｆｕｎｄｉｎｇ ｐｒｏｇｒａｍ： Ｈａｉｎａｎ Ｈｅａｌｔｈ ａｎｄ Ｆａｍｉｌｙ Ｐｌａｎｎｉｎｇ Ｉｎｄｕｓｔｒｙ Ｓｃｉｅｎｔｉｆｉｃ Ｒｅｓｅａｒｃｈ Ｐｒｏｊｅｃｔ （１８Ａ２０００７３）

Abstract：

Objective To analyze the correlation between the expression of ubiquitin binding enzyme variant 1A(UEV1A), ubiquitin ligase E2N(UBE2N) and the expression of epithelial mesenchymal transformation(EMT) gene in breast cancer and its clinical prognostic significance.Methods One hundred and twenty-four breast cancer patients diagnosed and treated by Qionghai People's Hospital/Hainan Eastern Regional Medical Center from February 2016 to February 2017 were selected as the study subjects. The expressions of UEV1A, UBE2N and EMT pathway genes E-cadherin(E-cad), N-cadherin(N-cad), vim and Snail mRNA in breast cancer tissues and adjacent tissues were detected by real-time fluorescent quantitative PCR; Immunohistochemical method was used to detect the levels of UEV1A and UBE2N proteins in tissues. To compare the difference of UEV1A and UBE2N protein levels in breast cancer patients with different clinicopathological characteristics. Pearson correlation analysis and Spearman rank correlation analysis were used to analyze the correlation between UEV1A, UBE2N mRNA and EMT related gene expression in breast cancer tissues, as well as the correlation between UEV1A and UBE2N protein levels in cancer tissues. Kaplan Meier survival analysis: The impact of UEV1A and UBE2N protein levels on the survival and prognosis of breast cancer patients. Multivariate Cox regression analysis of factors affecting the survival and prognosis of breast cancer patients.Results UEV1A, UBE2N, N-cad, Vim, and Snail mRNA expression in breast cancer tissues were higher than those in adjacent noncancerous tissues, while E-cad mRNA expression was lower than that in adjacent noncancerous tissues(t/P=28.803/<0.001, 48.654/<0.001, 54.411/<0.001, 46.213/<0.001, 27.273/<0.001, 22.228/<0.001). UEV1A and UBE2N mRNA expression were positively correlated with N-cad, Vim, and Snail mRNA expression in cancer tissues(UEV1A:r=0.694, 0.702, 0.806,P<0.001 for all; UBE2N:r=0.717, 0.756, 0.803,P<0.001 for all), and negatively correlated with E-cad mRNA expression(r=-0.741,-0.756,P<0.001 for both). The positive expression rate of UEV1A and UBE2N proteins in breast cancer tissues was significantly higher than that in adjacent noncancerous tissues(χ²/P=68.896/<0.001, 64.851/<0.001); there was a significant positive correlation between UEV1A and UBE2N protein expression in cancer tissues(r/P=0.785/<0.001). The positive expression rate of UEV1A and UBE2N proteins in breast cancer tissues was higher in patients with T2-4 stage and lymph node metastasis than in those with T1 stage and without lymph node metastasis(UEV1A:χ²/P=29.803/<0.001, 4.015/0.045; UBE2N: χ²/P=7.038/0.008, 8.572/0.003). Breast cancer patients with positive UEV1A expression had a lower 5-year overall survival rate than those with negative expression(χ²/P=5.085/0.024), and those with positive UBE2N expression had a lower 5-year overall survival rate than those with negative expression(χ²/P=8.391/0.004). T2-4 stage, lymph node metastasis, positive UEV1A expression, and positive UBE2N expression were independent risk factors affecting the survival prognosis of breast cancer patients [OR(95%CI)=1.777(1.299-2.432), 1.613(1.193-2.181), 1.838(1.302-2.596), 1.735(1.224-2.459),P<0.001 for all].Conclusion The expression of UEV1A and UBE2N in breast cancer tissue is increased, which are related to tumor stage and lymph node metastasis, and are independent risk factors affecting the prognosis of breast cancer patients.