β-Catenin Expression Negatively Correlates with WIF1 and Predicts Poor Clinical Outcomes in Patients with Cervical Cancer

Abstract

Aberrant activation of the canonical Wnt pathway plays a significant role in cervical cancer (CC). However, limited data show the correlation between the cancer clinicopathological characteristics and the key molecules such as β-catenin and Wnt inhibitory factor 1 (WIF1). In this study, β-catenin and WIF1 expression were analyzed by immunohistochemistry for 196 patients with CC, 39 with cervical intraepithelial neoplasia (CIN), and 41 with normal cervical epithelium (NCE). Significant overexpression of β-catenin was detected in CC (67.9%) when compared to CIN (43.6%) or NCE (34.1%), p < 0.01, while low WIF1 expression was detected in CC (24.0%) when compared to CIN (59.0%) or NCE (58.5%), p < 0.001. Negative correlation was shown between β-catenin and WIF1 expression (r = −0.637, p < 0.001). In addition, multivariate analysis revealed that both lymph node metastasis and β-catenin expression were the independent prognostic factors not only for disease-free survival (HR = 5.029, p < 0.001; HR = 2.588, p = 0.035, resp.), but also for overall survival (HR = 5.058, p < 0.001; HR = 2.873, p = 0.031, resp.). Our findings indicate that, besides lymph node metastasis, β-catenin expression may also be a poor prognostic factor for CC while WIF1 could be a potential drug target for treatment of advanced CC.

Galectin-3 and &beta;-catenin are associated with a poor prognosis in serous epithelial ovarian cancer

“… 13 β-catenin staining was evaluated according to Maruyama’s method. 14 , 15 If >10% of cancer cells were positively stained in the cytoplasm and/or nuclei, the cells were considered β-catenin positive. In contrast, cancer cells with only membranous staining were considered β-catenin negative.…”

Association of low expression of E‑cadherin and β‑catenin with the progression of early stage human squamous cervical cancer

“…EMT in SCC and evidence from surgical specimens of SCC suggests that SCC progression is accompanied by E-cadherin downregulation and vimentin upregulation (18)(19)(20)(21). HPV16 E6 or E7 have been indicated to regulate EMT in cervical epithelial cells, therefore, promoting tumor progression and metastasis (22,23).…”

FEZF1 is an Independent Predictive Factor for Recurrence and Promotes Cell Proliferation and Migration in Cervical Cancer

“…The Wnt signaling pathway controls body axis patterning, cell fate specification, cell proliferation and cell migration during development, and aberrant activation of this pathway has been implicated in the development of many types of human cancers 19 - 21 , including cervical cancer 22 . Increase of β-catenin, the hallmark of canonical Wnt pathway activation, has been reported to be an independent prognostic factor for the RFS and OS of cervical cancer patients 23 . Although FEZF1 does not bind to CTNNB1 gene directly, many upstream pathway genes and several genes that control β-catenin stability are FEZF1 targets (Figure 5 B).…”