Overexpression of Wnt7α protein predicts poor survival in patients with colorectal carcinoma
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Wnt7α (wingless-type MMTV integration site family, member 7A) is a secreted glycoprotein that plays a critical role in tumorigenesis and development by controlling cell proliferation and differentiation. Whether Wnt7α has the properties of an oncogene or not is an interesting issue because of its diverse expression in different tumors. In the present study, Wnt7α protein expression was evaluated through immunohistochemistry and Western blot analysis. Univariate and multivariate analyses were applied to explore the associations between Wnt7α staining score and various clinical parameters, including overall survival (OS) and disease-free survival (DFS), and a total of 212 patients with colorectal cancer (CRC) were surveyed. Wnt7α was strongly expressed in most CRC tissues but weakly expressed in adjacent normal mucosa, colorectal adenomas, and colonic polyps. High levels of Wnt7α expression were strongly associated with tumor size (P = 0.006), lymph node involvement (P < 0.001), and the international tumor–node–metastasis (TNM) stage (P = 0.005). Patients with strong Wnt7α expression showed significantly poorer OS and DFS than patients with weak Wnt7α expression (P < 0.0001, both). Multivariate Cox analysis confirmed that Wnt7α protein expression and TNM stage are independent factors of adverse OS and DFS in CRC patients. Taken together, our results present evidence that Wnt7α overexpression is associated with an unfavorable prognosis and that positive Wnt7α, in addition to TNM stage, may be an independent prognosis factor influencing OS and DFS prediction in CRC patients.
KeywordsColorectal cancer Wnt7α Prognosis Immunohistochemistry
This study was supported by grants from the National Natural Science Foundation of China (No. 81372612), the Heilongjiang Province Outstanding Youth Science Fund, and the Study Abroad Returnees Science Foundation of Heilongjiang (Nos. LC201109, JC201203).
Conflicts of interest
- 30.Winn RA, Marek L, Han SY, Rodriguez K, Rodriguez N, Hammond M, et al. Restoration of Wnt-7a expression reverses non-small cell lung cancer cellular transformation through frizzled-9-mediated growth inhibition and promotion of cell differentiation. J Biol Chem. 2005;280:19625–34.CrossRefPubMedGoogle Scholar
- 31.Winn RA, Van Scoyk M, Hammond M, Rodriguez K, Crossno Jr JT, Heasley LE, et al. Antitumorigenic effect of Wnt 7a and Fzd 9 in non-small cell lung cancer cells is mediated through ERK-5-dependent activation of peroxisome proliferator-activated receptor gamma. J Biol Chem. 2005;281:26943–50.CrossRefGoogle Scholar
- 34.Ochoa-Hernández AB, Ramos-Solano M, Meza-Canales ID, García-Castro B, Rosales-Reynoso MA, Rosales-Aviña JA, et al. Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation. BMC Cancer. 2012;12:60.CrossRefPubMedPubMedCentralGoogle Scholar