High expression levels of Wnt5a and Ror2 in laryngeal squamous cell carcinoma are associated with poor prognosis

Abstract

The present study investigated the prognostic significance of Wnt family member 5a (Wnt5a) and receptor tyrosine kinase-like orphan receptor 2 (Ror2) expression in laryngeal squamous cell carcinoma (LSCC). The protein expression levels of Wnt5a and Ror2 were analyzed in specimens from 137 patients with LSCC, using immunohistochemical staining of tissue microarrays and pairs of LSCC and adjacent tissue samples, and examined the associations between the two markers and various clinicopathological parameters. The Wnt5a and Ror2 expression levels were significantly higher in LSCC tissues than in normal tissue samples (Wnt5a, P=0.015; Ror2, P=0.039), and were significantly associated with high tumor stage (P<0.001), lymph node metastasis (Wnt5a, P=0.029; Ror2, P=0.018), and with each other (P=0.002). Patients with LSCC with high Wnt5a or Ror2 expression had poorer prognosis compared with those with low Wnt5a (P=0.022) or Ror2 (P=0.038) expression. Thus, Wnt5a and Ror2 may affect LSCC development, and are potential biomarkers in LSCC.

Keywords: Wnt family member 5a; immunohistochemistry; laryngeal squamous cell carcinoma; prognosis; receptor tyrosine kinase-like orphan receptor 2.

Figure 1.

Representation of Wnt5a and Ror2 protein expression in LSCC and tumor-adjacent normal tissue on tissue microarray sections. (A) LSCC with high Wnt5a and Ror2 expression. (B) LSCC with no Wnt5a or Ror2 expression. (C) Tumor-adjacent normal tissue with no Wnt5a expression or Ror2 expression. Wnt5a and Ror2 staining are each shown at ×40 and ×400 magnification, with hematoxylin counterstaining. Wnt5a, Wnt family member 5a; Ror2, receptor tyrosine kinase-like orphan receptor 2; LSCC, laryngeal squamous cell carcinoma.

Figure 2.

Survival curves of laryngeal squamous cell carcinoma determined using the Kaplan-Meier estimator method and the log-rank test. Overall survival curves are shown for (A) Wnt5a⁺ (green line, 1) and Wnt5a⁻ (blue line, 0), patients in the high-expression group (Wnt5a⁺) had significantly poorer prognosis compared with those in the low-expression group (Wnt5a; P=0.020, log-rank test); (B) Ror2⁺ (green line, 1) and Ror2⁻ (blue line, 0), patients in the high-expression group (Ror2⁺) had significantly poorer prognosis compared with those in the low-expression group (Ror2; P=0.001, log-rank test); and (C) Wnt5a⁺/Ror2⁺ (red line, 2), Wnt5a⁺/Ror2⁻ or Wnt5a⁻/Ror2⁺ (green line, 1) and Wnt5a⁻/Ror2⁻ (blue line, 0), patients in the high Wnt5a and high Ror2 expression group (Wnt5a⁺/Ror2⁺) had significantly poorer prognosis compared with both those in the high Wnt5a or high Ror2 expression group (Wnt5a⁺/Ror2⁻ or Wnt5a⁻/Ror2⁺) and those in the low-expression group (Wnt5a⁻/Ror2; P=0.001, log-rank test). Wnt5a, Wnt family member 5a; Ror2, receptor tyrosine kinase-like orphan receptor 2.