Expression of Wntless in colorectal carcinomas is associated with invasion, metastasis, and poor survival

Abstract

Wntless also known as WLS, GPR177, or Evi, is a key modulator of Wnt protein secretion. Its overexpression is found in certain types of human cancers such as malignant astrocytoma and breast cancers. We hypothesized that this protein may be aberrantly expressed in colorectal carcinoma which also possesses aberrant Wnt signaling. To investigate the association between the expression of Wnt and clinicopathological parameters in colorectal carcinomas, a set of colorectal carcinoma tissue samples was analyzed for the expression of WLS using an anti-GPR177 monoclonal antibody specific for the WLS protein. High expression of WLS protein was observed in most colorectal carcinoma samples compared with nontumor mucosa in the same patients (117/201, 58.2%). High expression of WLS was associated with sex (p = 0.005), age (p = 0.009), depth of invasion (p < 0.001), lymph node metastasis (p = 0.026), and tumor-node-metastasis (TNM) stage (p = 0.003). No significant relationship between the expression of WLS and tumor location, size, and differentiation was found. The survival analyses showed WLS was an independent prognostic marker and that patients whose carcinoma exhibited high expression of WLS had a poorer outcome (p = 0.033). Our results indicate that WLS may play a role in invasion and metastasis of colorectal carcinoma. The WLS protein expression level may be used as a potential prognostic marker in colorectal carcinoma. Furthermore, the WLS gene may provide a novel target for therapy of colorectal carcinoma.

High expression of Wls is associated with lymph node metastasis and advanced TNM stage in gastric carcinomas

“…Immuohistochemistry for Wls was performed using a routine protocol as we described previously . In brief, formalin‐fixed, paraffin‐embedded samples were sectioned at 4 μm thickness.…”

“…Immuohistochemistry for Wls was performed using a routine protocol as we described previously. 21 In brief, formalinfixed, paraffin-embedded samples were sectioned at 4 mm thickness. The sections were deparaffinized using xylene, dehydrated by an ethanol gradient, and then rehydrated with deionized water.…”

“…The expression level and the roles of Wls in some types of human cancers have been studied, including malignant astrocytomas, breast cancer, and ovarian cancer . We previously detected expression of Wls in colorectal carcinomas and found that expression of Wls is associated with invasion, metastasis, and poor survival in colorectal carcinoma . To our knowledge, the expression level of Wls in gastric carcinoma and its correlation with clinicopathological variants have not been well investigated.…”

“…[18][19][20] We previously detected expression of Wls in colorectal carcinomas and found that expression of Wls is associated with invasion, metastasis, and poor survival in colorectal carcinoma. 21 To our knowledge, the expression level of Wls in gastric carcinoma and its correlation with clinicopathological variants have not been well investigated. In this study, we detected the expression of Wls in a set of gastric carcinoma specimens by immunohistochemstry, and analyzed the relationship between the expression of Wls and clinicopathological parameters.…”

Wntless Is Highly Expressed in Advanced-Stage Intrahepatic Cholangiocarcinoma

“…High expression of Wls in gastric cancer was positively associated with well-differentiated tumor, lymph node metastasis, and advanced TNM stage. High expression of Wls was also observed in most colorectal cancers, and was related to sex, depth of invasion, lymph node metastasis, and TNM stage (Xu et al 2016). More recently, we investigated Wls expression in hepatocellular carcinoma (HCC) and its clinicapathological significances (Zhou et al 2017).…”