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KIF14 Messenger RNA Expression Is Independently Prognostic for Outcome in Lung Cancer

Authors' Affiliations: ¹ Division of Applied Molecular Oncology and ² Clinical Studies Resource Centre, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network; ³ Division of Medical Oncology and Hematology, Department of Medicine, University Health Network; and Departments of ⁴ Molecular and Medical Genetics, ⁵ Medical Biophysics, ⁶ Medicine, ⁷ Laboratory Medicine and Pathobiology, and ⁸ Ophthalmology, University of Toronto, Toronto, Ontario, Canada

Requests for reprints: Brenda L. Gallie, Division of Applied Molecular Oncology, Room 8-415, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. Phone: 416-946-2324; Fax: 416-946-4619; E-mail: gallie{at}attglobal.net.

Purpose: The mitotic kinesin KIF14 is overexpressed in multiple cancers including lung cancer. Therefore, we investigated KIF14 expression in association with clinical variables and the effect of KIF14 on in vitro colony formation in non–small-cell lung carcinoma.

Experimental Design: RNA was extracted from 129 untreated, resected tumors and KIF14 expression was quantified by real-time reverse transcription-PCR. Associations with clinical variables were determined by standard statistical methods. KIF14 expression was knocked down by small interfering RNA in H1299 and HeLa cells; proliferation and growth in soft agar were assayed.

Results: Squamous cell carcinoma had the highest KIF14 level, followed by large-cell undifferentiated carcinoma, then adenocarcinoma (P = 0.002). KIF14 level decreased with differentiation (P = 0.01) but was not associated with pathologic stage, T or N stage, or sex. When dichotomized about the median, KIF14 overexpression significantly decreased disease-free survival (Kaplan-Meier log-rank, P = 0.01) and trended toward decreasing overall survival (P = 0.08). In a univariate Cox proportional hazard regression, increasing KIF14 expression decreased disease-free survival [P = 0.01; hazard ratio, 1.44 (95% confidence interval, 1.09-1.91)]. In a multivariate Cox regression, including stage, differentiation, histology, and tumor purity as covariates, KIF14 overexpression remained an independent prognostic factor for disease-free survival [P = 0.01; hazard ratio, 1.45 (95% confidence interval, 1.09-1.94)]. Knockdown of KIF14 in non–small-cell lung carcinoma and cervical carcinoma cell lines decreased proliferation and colony formation in soft agar.

Conclusions: KIF14 expression is independently prognostic for disease-free survival in lung cancer and knockdown decreases tumorigenicity in vitro, showing that it is a clinically relevant oncogene and an exciting therapeutic target for further study.

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