Overexpression of Wnt5a Promotes Angiogenesis in NSCLC

Abstract

To evaluate Wnt5a expression and its role in angiogenesis of non-small-cell lung cancer (NSCLC), immunohistochemistry and CD31/PAS double staining were performed to examine the Wnt5a expression and we analyze the relationships between Wnt5a and microvessel density (MVD), vasculogenic mimicry (VM), and some related proteins. About 61.95% of cases of 205 NSCLC specimens exhibited high expression of Wnt5a. Wnt5a expression level was upregulated in the majority of NSCLC tissues, especially in squamous cell carcinoma, while its expression level in adenocarcinoma was the lowest. Wnt5a was also found more frequently expressed in male patients than in female patients. Except for histological classification and gender, little association was found between Wnt5a and clinicopathological features. Moreover, Wnt5a was significantly correlated with prognosis. Overall, Wnt5a-positive expression in patients with NSCLC indicated shorter survival time. As for vascularization in NSCLC, Wnt5a showed close association with VM and MVD. In addition, Wnt5a was positively related with β-catenin-nu, VE-cadherin, MMP2, and MMP9. The results demonstrated that overexpression of Wnt5a may play an important role in NSCLC angiogenesis and it may function via canonical Wnt signal pathway. This study will provide evidence for further research on NSCLC and also will provide new possible target for NSCLC diagnosis and therapeutic strategies.

Notch and Wnt signaling pathway in cancer: Crucial role and potential therapeutic targets (Review)

“…Furthermore, Chu et al (11) reported that nuclear factorkappa B also influences the prognosis of oral squamous cell carcinoma. In addition, Wnt5a positivity was reported as a sign of short survival period in NSCLC (12). We can conclude from these data that signaling pathways may be unique prognosis markers for certain cancer types, and may also provide clues for further research on mechanism of cancer prognosis.…”

Prognostic value of wingless-type proteins in non-small cell lung cancer patients: a meta-analysis

“…Canonical Wnt signaling activation via the Frizzled family of receptors will finally contribute to the promotion of tumorigenesis through the expression of its target genes, such as Cyclin D1 and c-Myc (31,32). Xu et al (13) showed that Wnt1 expression was significantly associated with those of β-catenin and c-Myc in NSCLC; Nakashima et al (23) found that Wnt3 expression in NSCLC was associated with c-Myc expression and tumor progression; Yao et al (14) reported that Wnt5a contributes to NSCLC progression through the promotion of angiogenesis. Together these facts indicate that Wnt1, Wnt3 and Wnt5a are able to promote lung carcinogenesis.…”

“…Flow diagram of the study selection in our meta-analysis is shown in Figure 1. (13,(19)(20)(21)(22), and three studies on Wnt5a (14,18,24), and two studies the role of Wnt2 (25) and Wnt3 (23) respectively.…”

“…The subgroup analysis was performed by Wnt protein type. Five studies were found to investigate the role of Wnt1 (13,(19)(20)(21)(22), two studies the role of Wnt2 (25) and Wnt3 (23) respectively and three studies the role of Wnt5a (14,18,24). Higher Wnt1 expression and Wnt5a expression were associated with poorer OS, as the pooled HR for OS was 1.69 (95% CI: 1.34-2.14) and 1.68 (95% CI: 1.32-2.13), respectively ( Figure 3).…”

“…Xu et al (13) found that Wnt1-positive expression in patients with NSCLC was closely associated with short overall survival (OS). Yao et al (14) showed that high level of Wnt5a expression was also related to poor outcomes among NSCLC patients.…”