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Int J Clin Exp Pathol 2013;6(4):598-612

Original Article
FER overexpression is associated with poor postoperative prognosis and cancer-cell
survival in non-small cell lung cancer

Masanori Kawakami, Shigeki Morita, Mitsuhiro Sunohara, Yosuke Amano, Rie Ishikawa, Kousuke Watanabe, Emi Hamano, Nobuya Ohishi,
Jun Nakajima, Yutaka Yatomi, Takahide Nagase, Masashi Fukayama, Daiya Takai

Department of Respiratory Medicine, Clinical Laboratory, Pathology and Cardiothoracic Surgery, The University of Tokyo Hospital, Tokyo
113-8655, Japan

Received January 4, 2013; Accepted February 16, 2013; Epub March 15, 2013; Published April 1, 2013

Abstract: Here, we show that overexpression of fer tyrosine kinase (FER), a non-receptor tyrosine kinase, predicts poor postoperative outcome
and might be involved in cancer-cell survival in non-small cell lung cancer (NSCLC). Systematic screening using in silico analyses and
quantitative RT-PCR revealed that FER was overexpressed in about 10% of NSCLC patients. Evaluation of FER expression using
immunohistochemistry (IHC) on tissue microarrays was consistent with the mRNA level detected using quantitative RT-PCR. In analyses of
135 NSCLC patients who had undergone potential curative resection, we found that FER overexpression detected using IHC had no
association with clinicopathological features such as age, sex, smoking history, histological type, disease stage, T factor, N factor, adjuvant
chemotherapy history, or EGFR mutation, but was correlated with poor postoperative survival periods. A multivariate Cox regression analysis
showed that this prognostic impact was independent of other clinicopathological features. In functional analyses of FER in vitro, FER exhibited
a transforming activity, suggesting that it possesses oncogenic functions. We also found that human lung cancer NCI-H661 cells, which
exhibited FER-outlier expression, were led to apoptosis by the knockdown of FER using RNA interference. FER overexpression might serve as
a prognostic biomarker and be involved in cancer-cell survival in NSCLC. (IJCEP1301003).

Keywords: Non-small cell lung cancer, FER overexpression, prognostic factor

Address correspondence to: Dr. Daiya Takai, Department of Clinical Laboratory, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku,
Tokyo, 113-8655, Japan. Tel: +81-3-3815-5411; Fax: +81-3-5689-0495; E-mail: dtakai-ind@umin.ac.jp