Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2019; 10:5726-5726.

Overexpression of CTEN relates to tumor malignant potential and poor outcomes of adenocarcinoma of the esophagogastric junction

Kenichi Aratani, Shuhei Komatsu _, Daisuke Ichikawa, Takuma Ohashi, Mahito Miyamae, Wataru Okajima, Taisuke Imamura, Jun Kiuchi, Keiji Nishibeppu, Toshiyuki Kosuga, Hirotaka Konishi, Atsushi Shiozaki, Hitoshi Fujiwara, Kazuma Okamoto, Hitoshi Tsuda and Eigo Otsuji

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Oncotarget. 2017; 8:84112-84122. https://doi.org/10.18632/oncotarget.21109

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Abstract

Kenichi Aratani1,*, Shuhei Komatsu1,*, Daisuke Ichikawa1, Takuma Ohashi1, Mahito Miyamae1, Wataru Okajima1, Taisuke Imamura1, Jun Kiuchi1, Keiji Nishibeppu1, Toshiyuki Kosuga1, Hirotaka Konishi1, Atsushi Shiozaki1, Hitoshi Fujiwara1, Kazuma Okamoto1, Hitoshi Tsuda2,3 and Eigo Otsuji1

1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan

2Department of Pathology, National Cancer Center Hospital, Tokyo, Japan

3Department of Basic Pathology, National Defense Medical College, Saitama, Japan

*These authors contributed equally to this work

Correspondence to:

Shuhei Komatsu, email: [email protected]

Keywords: adenocarcinoma of the esophagogastric junction, gastric cancer, CTEN, prognosis, oncogene

Received: April 19, 2017     Accepted: September 04, 2017     Published: September 20, 2017

ABSTRACT

Background: To detect a novel treatment target for adenocarcinoma of the esophagogastric junction (AEG), we tested whether C-terminal tensin-like (CTEN), a member of the tensin gene family and frequently overexpressed in various cancers, acts as a cancer-promoting gene through overexpression in AEG.

Materials and Methods: We analyzed 5 gastric adenocarcinoma (GC) cell lines and 104 primary AEG tumors curatively resected in our hospital between 2000 and 2010.

Results: CTEN overexpression was detected in GC cell lines (2/5 cell lines; 40%) and primary AEG tumor samples (35/104 cases; 34%). CTEN knockdown using several specific siRNAs inhibited the proliferation, migration, and invasion of CTEN-overexpressing cells. CTEN overexpression was significantly correlated with more aggressive venous and lymphatic invasion, deeper tumor depth, and higher rates of lymph node metastasis and recurrence. Patients with CTEN-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P < 0.0001, log-rank test) in an expression-dependent manner. CTEN positivity was independently associated with a worse outcome in the multivariate analysis (P = 0.0423, hazard ratio 3.54 [1.04–16.4]).

Conclusions: CTEN plays a crucial role in tumor cell proliferation, migration, and invasion through its overexpression, which highlights its usefulness as a prognosticator and potential therapeutic target in AEG.


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