title: FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer.
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.
authors.affiliation: Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawakami
authors.forename: Shigeki
authors.initials: S
authors.lastname: Morita
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Sunohara
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Amano
authors.forename: Rie
authors.initials: R
authors.lastname: Ishikawa
authors.forename: Kousuke
authors.initials: K
authors.lastname: Watanabe
authors.forename: Emi
authors.initials: E
authors.lastname: Hamano
authors.forename: Nobuya
authors.initials: N
authors.lastname: Ohishi
authors.forename: Jun
authors.initials: J
authors.lastname: Nakajima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Daiya
authors.initials: D
authors.lastname: Takai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D012044:Regression Analysis; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases
keywords: FER overexpression; Non-small cell lung cancer; prognostic factor