TNK2 gene amplification is a novel predictor of a poor prognosis in patients with gastric cancer
Corresponding Author
Kazuya Shinmura MD, PhD
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Correspondence to: Kazuya Shinmura, MD, PhD, Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka 431-3192, Japan.
Fax: +81-53-435-2225. E-mail: [email protected]
Search for more papers by this authorShinichiro Kiyose BS
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorKiyoko Nagura BS
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorHisaki Igarashi BS
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorYusuke Inoue MD
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorSatoki Nakamura MD, PhD
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorMatsuyoshi Maeda MD, PhD
Department of Pathology, Toyohashi Municipal Hospital, Toyohashi, Japan
Search for more papers by this authorMegumi Baba MD, PhD
Department of Surgery 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorHiroyuki Konno MD, PhD
Department of Surgery 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorHaruhiko Sugimura MD, PhD
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorCorresponding Author
Kazuya Shinmura MD, PhD
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Correspondence to: Kazuya Shinmura, MD, PhD, Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka 431-3192, Japan.
Fax: +81-53-435-2225. E-mail: [email protected]
Search for more papers by this authorShinichiro Kiyose BS
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorKiyoko Nagura BS
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorHisaki Igarashi BS
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorYusuke Inoue MD
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorSatoki Nakamura MD, PhD
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorMatsuyoshi Maeda MD, PhD
Department of Pathology, Toyohashi Municipal Hospital, Toyohashi, Japan
Search for more papers by this authorMegumi Baba MD, PhD
Department of Surgery 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorHiroyuki Konno MD, PhD
Department of Surgery 2, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorHaruhiko Sugimura MD, PhD
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
Search for more papers by this authorAbstract
Backgrounds and Objectives
We previously examined the amplification status of 10 kinase genes (PIK3CA, EPHB3, TNK2, PTK7, EGFR, MET, ERBB2, HCK, SRC, and AURKA) in gastric cancer (GC). This study aimed to determine the prognostic significance of these gene amplifications in GC.
Methods
A survival analysis was performed for GC patients. Since TNK2 amplification was identified as a prognostic marker in the analysis, we also examined the functional effect of TNK2 overexpression on gastric cells.
Results
A Kaplan–Meier analysis showed that the prognosis of patients with GC exhibiting TNK2 or AURKA amplification was significantly poorer than the prognosis of patients with GC without TNK2 or AURKA amplification. A further multivariate analysis revealed that TNK2 amplification was an independent predictor of a poor survival outcome among patients with GC (hazard ratio, 3.668; 95% confidence interval, 1.513–7.968; P = 0.0056). TNK2-overexpressing GC cells showed an increase in cell migration and non-anchored cell growth. Finally, microarray and pathway analyses revealed the aberrant regulation of some cancer-related pathways in TNK2-overexpressing GC cells.
Conclusions
These results suggested that TNK2 amplification is an independent predictor of a poor prognosis in patients with GC and leads to an increase in the malignant potential of GC cells. J. Surg. Oncol. 2014 109:189–197. © 2013 Wiley Periodicals, Inc.
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