Aberrant expression of UBE2C in endometrial cancer and its correlation to epithelial mesenchymal transition

Abstract

Ubiquitin-conjugating enzyme E2C (UBE2C), its overexpression promotes tumor progression, is a key component of the ubiquitin conjugating proteasome complex. Epithelial-mesenchymal transition, which is lost epithelial features and gained mesenchymal features in some epithelial cancers, is involved in epithelial cancers' invasiveness and metastasis. The aim of this study is to detect the expression of UBE2C, WNT5α, and E-cad in endometrial cancer (EC) and their clinical significance. The expression of UBE2C, WNT5α, and ZEB1 in 125 cases EC tissues were detected by immunohistochemistry. Patients clinicopathological, demography, and follow-up data were also collected. Positive rates of expression of UBE2C and ZEB1 were significantly higher in EC tissues when compared with the control tissues. The positive expression of UBE2C and ZEB1 were positively associated with tumor stages, local lymph node metastasis, and International Federation of Gynecology and Obstetrics (FIGO) stages. The positive rate of expression of WNT5a was significantly lower in EC tissues when compared with the control tissues. And positive expression of E-cad was inversely related to tumor stages, lymph node metastasis stages, and FIGO stages. Kaplan-Meier analyses demonstrated that positive expression of UBE2C or ZEB1 for EC patients had unfavorably overall survival time when compared with patients with negative expression of UBE2C or ZEB1. And EC patients with positive expression of WNT5a had favorably overall survival time when compared with EC patients with negative expression of WNT5a. Multivariate analysis demonstrated that positive expression UBE2C, WNT5α, and ZEB1, as well as FIGO stages were independent prognostic factors for EC patients. UBE2C, ZEB1, and WNT5a should be considered promising biomarkers for EC patients' prognosis.

Figure 1.

Immunostaining of UBE2C or ZEB1 or Wnt5a in EC or the control tissues. A: Positive staining of UBE2C in nuclei of the EC cells (400 magnification); B: Negative staining of UBE2C in the control tissues (400); C: Positive staining of ZEB1 in the nuclei of the EC cells (200); D: Negative staining of ZEB1 in the control cells (400). E: Negative staining of Wnt5a in the EC cells (400); F: Positive staining of Wnt5a in the cytoplasm of the control cells (400). EC = endometrial cancer, UBE2C = ubiquitin-conjugating enzyme E2C, WNT5a = wingless MMTV integration site 5a, ZEB1 = Zinc finger E-box binding homeobox1.

Figure 2.

Kaplan–Meier analysis of the survival rate of patients with EC. The y-axis represents the percentage of patients; the x-axis represents their survival in months. A: Overall survival (OS) of all patients in relation to UBE2C (log-rank = 28.069, P < .001); B: OS of all patients in relation to ZEB1 expression (log-rank = 29.902, P < .001); C: OS of all patients in relation to Wnt5a (log-rank = 33.955, P < .001). In A–C analyses, the green line represents patients with positive expression of biomarkers and the blue line representing the negative expression of biomarkers. EC = endometrial cancer, UBE2C = ubiquitin-conjugating enzyme E2C, WNT5a = wingless MMTV integration site 5a, ZEB1 = Zinc finger E-box binding homeobox1.