Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients.
The Wnt family genes encode multifunctional signaling glycoproteins that are involved in the regulation of a wide variety of normal and pathological processes including tumorigenesis. In order to clarify the clinical significance of the intratumoral Wnt1 expression in non-small cell lung cancer (NSCLC), we performed an immunohistochemical study on the Wnt1 expression in NSCLCs in relation to the tumor proliferation. The intratumoral Wnt1 protein expression appeared in a cytoplasmic staining pattern. Of the 151 NSCLCs studied, 61 carcinomas (40.4%) were Wnt1-positive. Regarding the tumor biology of the intratumoral Wnt1 expression, the Ki-67 proliferation index was significantly higher in Wnt1-positive than in Wnt1-negative tumors (P=0.0062). Furthermore, regarding the expression of c-Myc, one of the proliferation-regulating Wnt targets, the percentage of c-Myc-positive tumor cells was significantly higher in Wnt1-positive than in Wnt1-negative tumors (P=0.0019). The Ki-67 proliferation index was significantly higher in c-Myc-positive than in c-Myc-negative tumors (P=0.0239). The overall survival was significantly lower in patients with Wnt1-positive NSCLCs than in patients with Wnt1-negative NSCLCs (P=0.0003). A Cox regression analysis demonstrated that the Wnt1 status was a significant prognostic factor for NSCLC patients (hazard ratio 1.983; P=0.0061). Our results revealed that the Wnt1 overexpression affects the tumor proliferation in NSCLCs, partly via the upregulation of c-Myc.
Nakashima
Takashi
T
Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
Liu
Dage
D
Nakano
Jun
J
Ishikawa
Shinya
S
Yokomise
Hiroyasu
H
Ueno
Masaki
M
Kadota
Kyuichi
K
Huang
Cheng-Long
CL
D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051155:Wnt1 Protein / Q000378:metabolism*
D019394:Ki-67 Antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C495247:WNT1 protein, human; D051155:Wnt1 Protein