Intratumoral Wnt2B expression affects tumor proliferation and survival in malignant pleural mesothelioma patients

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive thoracic tumor with a poor prognosis. We performed a comprehensive clinical study on the intratumoral expression of Wnt1, Wnt2B and Wnt5A in MPM. One hundred and seven MPM patients were investigated. Immunohistochemistry was performed to evaluate the intratumoral expression of Wnt1, Wnt2B, Wnt5A, survivin and c-Myc, and the Ki-67 proliferation index. The apoptotic index was evaluated by the TUNEL method. Among the 107 MPMs, 23 MPMs (21.5%) were Wnt1-high tumors, 72 MPMs (67.3%) were Wnt2B-high tumors and 54 MPMs (50.5%) were Wnt5A-high tumors. There was no correlation among the levels of Wnt expression. The percentage of Wnt2B-positive tumors was significantly higher compared to that of the other Wnts (p<0.0001). Furthermore, intratumoral Wnt2B expression significantly correlated with the expression of survivin (p<0.001) and c-Myc (p<0.001). Regarding tumor biology, the Ki-67 proliferation index was significantly higher in the Wnt2B-high tumors than in the Wnt2B-low tumors (p=0.0438). In addition, the overall survival was significantly lower in patients with Wnt2B-high tumors than in those with Wnt2B-low tumors (p=0.0238). A Cox multivariate analysis also demonstrated the Wnt2B status to be a significant prognostic factor in MPM patients (p=0.0042). Intratumoral Wnt2B expression was associated with the expression of survivin and c-Myc, tumor proliferation and patient survival in MPM. Wnt2B is a potential molecular target for the treatment of Wnt2B-overexpressing MPMs.

Comparison of SKIP expression in malignant pleural mesotheliomas with Ki-67 proliferation index and prognostic parameters

“…In the multivariate Cox regression analysis, it was found that the factors affecting survival were SKIP expression intensity, Ki-67 proliferation index and non-epithelioid histological type. In previous studies, it was reported that the Ki-67 proliferation index was higher in MPM cases and that survival periods were shorter [9,14]. Similarly, the Ki-67 proliferation index was higher in non-epithelioid cases in our study.…”

“…Biomarkers such as survivin, fibulin-3 and mesothelin have also been suggested as prognostic factors to predict poor outcome in MPM, but they are not sufficient for use as prognostic biomarkers [8,9,10]. It is known that the Ki-67 proliferation index increases in MPM patients and that it is related to poor prognosis [9,14]. In HCC, alterations in SKIP expression and the Ki-67 proliferation index were found to be correlated, and it was reported that the increase of both of them is a short survey indicator in HCC patients [18].…”

“…Ki-67 is a monoclonal antibody developed against a nuclear antigen only available in proliferated cells. Determining Ki-67 expression levels has been demonstrated to be helpful in predicting the prognosis of breast cancer, prostate cancer and many other malignancies such as malign mesothelioma [12,13,14].…”

A crosstalk between TGF-β/Smad3 and Wnt/β-catenin pathways promotes vascular smooth muscle cell proliferation

“…Kobayashi et al demonstrate that Wnt2b plays a positive role in the proliferation of mesothelioma[28]. Similarly, Wang et al report that silencing Wnt2b significantly diminishes proliferation in several ovarian cancer cell lines[29].…”

miR-324-3p suppresses migration and invasion by targeting WNT2B in nasopharyngeal carcinoma

“…In head and neck squamous cell carcinoma, WNT2B played a role in tumourigenesis and chemotherapy resistance in vivo and in vitro [23]. Intratumoural WNT2B was reported to be correlated with the expression of Survivin and c-Myc, tumour proliferation and prognosis in malignant pleural mesothelioma [24]. Jiang et al also found that the high-expression level of WNT2B was associated with the progression and worse outcome of pancreatic cancer [25].…”