PMID- 28952025 OWN - NLM STAT- MEDLINE DCOM- 20180109 LR - 20181113 IS - 1432-1335 (Electronic) IS - 0171-5216 (Print) IS - 0171-5216 (Linking) VI - 144 IP - 1 DP - 2018 Jan TI - Pathological significance and prognostic significance of FES expression in bladder cancer vary according to tumor grade. PG - 21-31 LID - 10.1007/s00432-017-2524-1 [doi] AB - PURPOSE: The feline sarcoma oncogene protein (FES) is a non-receptor tyrosine kinase implicated in both oncogenesis and tumor suppression. Here, cancer cell lines and human tissues were employed to clarify the pathological and prognostic significance of FES in bladder cancer. METHODS: The relationship between FES expression and cancer aggressiveness was investigated using 3 cell lines (T24: corresponding to grade 3, 5637: corresponding to grade 2, and RT4: corresponding to grade 1) and 203 tissues derived from human bladder malignancies. Proliferation, invasion, and migration of cancer cells were assessed following the knockdown (KD) of FES expression by the siRNA method. Relationships between FES expression and pathological features, aggressiveness, and outcome were investigated. RESULTS: FES-KD inhibited the proliferation, migration, and invasion of T24 cells but not of RT4 cells and 5637 cells. Considering all patients, FES expression demonstrated a negative relationship with grade but no association with muscle invasion or cancer cell proliferation. However, it was positively correlated with pT stage and cell proliferation in high-grade tumors (p = 0.002); no such association was found for low-grade tumors. In addition, elevated FES expression was a negative prognostic indicator of metastasis after radical surgery for patients with high-grade tumors (p = 0.021) but not for those with low-grade malignancies. CONCLUSIONS: FES appeared to act as a suppressor of carcinogenesis, being associated with low tumor grade in the overall patient group. However, its expression correlated with cancer aggressiveness and poor outcome in high-grade bladder cancer. FES, therefore, represents a potential therapeutic target and useful prognostic factor for such patients. FAU - Asai, Akihiro AU - Asai A AD - Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Miyata, Yasuyoshi AU - Miyata Y AUID- ORCID: 0000-0001-6272-6657 AD - Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. int.doc.miya@m3.dion.ne.jp. FAU - Takehara, Kosuke AU - Takehara K AD - Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Kanda, Shigeru AU - Kanda S AD - Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Watanabe, Shin-Ichi AU - Watanabe SI AD - Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Greer, Peter A AU - Greer PA AD - Division of Cancer Biology and Genetics, Department of Pathology and Molecular Medicine, Queen's Cancer Research Institute, Queens University, Kingston, ON, K7L 3N6, Canada. FAU - Sakai, Hideki AU - Sakai H AD - Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. LA - eng GR - 15K10594/Japan Society for the Promotion of Science/ GR - 16K15690/Japan Society for the Promotion of Science/ PT - Journal Article DEP - 20170926 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.2 (FES protein, human) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-fes) SB - IM MH - Biomarkers, Tumor/*biosynthesis/genetics MH - Blotting, Western MH - Cell Line, Tumor MH - Cell Movement/physiology MH - Cell Proliferation/physiology MH - Female MH - Gene Knockdown Techniques MH - Humans MH - Immunohistochemistry MH - Male MH - Middle Aged MH - Neoplasm Grading MH - Neoplasm Invasiveness MH - Proto-Oncogene Proteins c-fes/*biosynthesis/genetics MH - Survival Rate MH - Urinary Bladder Neoplasms/genetics/*metabolism/pathology PMC - PMC5756570 OTO - NOTNLM OT - Bladder cancer OT - Cell proliferation OT - FES OT - Grade OT - Invasion OT - Prognosis COIS- FUNDING: This study was supported in part by a Grant-in-Aid from the Japan Society for the Promotion of Science (Grant nos. 15K10594 and 16K15690). CONFLICT OF INTEREST: The authors declare that they have no conflict of interest. ETHICAL APPROVAL: All procedures in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. INFORMED CONSENT: Informed consent was obtained from all individual participants included in this study. EDAT- 2017/09/28 06:00 MHDA- 2018/01/10 06:00 PMCR- 2017/09/26 CRDT- 2017/09/28 06:00 PHST- 2017/06/28 00:00 [received] PHST- 2017/09/17 00:00 [accepted] PHST- 2017/09/28 06:00 [pubmed] PHST- 2018/01/10 06:00 [medline] PHST- 2017/09/28 06:00 [entrez] PHST- 2017/09/26 00:00 [pmc-release] AID - 10.1007/s00432-017-2524-1 [pii] AID - 2524 [pii] AID - 10.1007/s00432-017-2524-1 [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2018 Jan;144(1):21-31. doi: 10.1007/s00432-017-2524-1. Epub 2017 Sep 26.