Intratumoral Wnt1 expression affects survivin gene expression in non-small cell lung cancer

Abstract

Survivin, a member of the inhibitor of apoptosis protein family, affects tumorigenesis. Recently, survivin is reported to be a target of the canonical Wnt pathway, which activates the transcription of various tumor-associated target genes. One hundred and twenty-two non-small cell lung cancers (NSCLCs) were investigated to evaluate survivin gene expression in relation to the expression of Wnt1 (a novel member of the canonical Wnt pathway) and Wnt5a (a novel member of the non-canonical Wnt pathway). The survivin gene expression was evaluated by semi-quantitative RT-PCR. The protein expression of pan-survivin, Wnt1, and Wn5a were investigated by immunohistochemistry. The apoptotic index and the Ki-67 proliferation index were also evaluated. Sixty-four tumors (52.5%) were survivin-high tumors, 65 tumors were Wnt1-high tumors, and 67 tumors (54.9%) were Wnt5a-high tumors. The standardized survivin gene expression significantly correlated with the apoptotic index (P<0.0001), the Ki-67 proliferation index (P<0.0001), and patient survival (P=0.0467). Furthermore, the percentage of Wnt1-positive tumor cells significantly correlated with the standardized survivin gene expression (P<0.0001). In contrast, the percentage of Wnt5a-positive tumor cells did not correlate with the standardized survivin gene expression. As a result, intratumoral Wnt1 expression significantly correlated with the apoptotic index (P<0.0001), the Ki-67 proliferation index (P<0.0001), and patient survival (P=0.0355). Intratumoral Wnt1 overexpression could produce more aggressive NSCLCs by induction of survivin.