TNK2 gene amplification is a novel predictor of a poor prognosis in patients with gastric cancer. Issue 3 (31st October 2013)

• Record Type: Journal Article
• Authors: Shinmura, Kazuya; Kiyose, Shinichiro; Nagura, Kiyoko; Igarashi, Hisaki; Inoue, Yusuke; Nakamura, Satoki; Maeda, Matsuyoshi; Baba, Megumi; Konno, Hiroyuki; Sugimura, Haruhiko
• Is Part Of: Journal of surgical oncology. Volume 109:Issue 3(2014:Mar. 01)
• Page Start: 189
• Page End: 197
• Publication Date: 2013-10-31
• Subjects: Cancer -- Surgery -- Periodicals; Neoplasms -- Periodicals; 616
• DOI: 10.1002/jso.23482
• Languages: English
• ISSNs: 0022-4790

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jso23482-sec-0001" sec-type="section"> <title>Backgrounds and Objectives</title> <p>We previously examined the amplification status of 10 kinase genes (<italic>PIK3CA</italic>, <italic>EPHB3</italic>, <italic>TNK2</italic>, <italic>PTK7</italic>, <italic>EGFR</italic>, <italic>MET</italic>, <italic>ERBB2</italic>, <italic>HCK</italic>, <italic>SRC</italic>, and <italic>AURKA</italic>) in gastric cancer (GC). This study aimed to determine the prognostic significance of these gene amplifications in GC.</p> </sec> <sec id="jso23482-sec-0002" sec-type="section"> <title>Methods</title> <p>A survival analysis was performed for GC patients. Since <italic>TNK2</italic> amplification was identified as a prognostic marker in the analysis, we also examined the functional effect of TNK2 overexpression on gastric cells.</p> </sec> <sec id="jso23482-sec-0003" sec-type="section"> <title>Results</title> <p>A Kaplan–Meier analysis showed that the prognosis of patients with GC exhibiting <italic>TNK2</italic> or <italic>AURKA</italic> amplification was significantly poorer than the prognosis of patients with GC without <italic>TNK2</italic> or <italic>AURKA</italic> amplification. A further multivariate analysis revealed that <italic>TNK2</italic> 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; <italic>P</italic> = 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.</p> </sec> <sec id="jso23482-sec-0004" sec-type="section"> <title>Conclusions</title> <p>These results suggested that <italic>TNK2</italic> 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. <italic>J. Surg. Oncol. 2014 109:189–197</italic>. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>