title: The level of RECQL1 expression is a prognostic factor for epithelial ovarian cancer.
abstract: BACKGROUND
  The human RECQ DNA helicase family is involved in genomic stability. Gene mutations of RECQL2, RECQL3, and RECQL4 are associated with genetic disorders and induce early aging and carcinogenesis. Although previous studies have reported that the level of RECQL1 expression is correlated with the prognosis of some of malignancies, the function of RECQL1 is not yet clarified. The present study aimed to examine the relationship between prognosis and the level of RECQL1 expression in epithelial ovarian cancer (EOC), and to identify the role of RECQL1 in EOC cells.
  
  
  METHODS
  The level of RECQL1 expression was determined immunohistochemically in 111 patients with EOC who received initial treatment at Hirosaki University hospital between 2006 and 2011. Effects of RECQL1 on cell growth or apoptosis were examined in vitro using wild-type and OVCAR-3 cells (RECQL1(+) cells) and similar cells transfected with RECQL1 siRNA transfected (RECQL1(-) cells).
  
  
  RESULTS
  The level of RECQL1 expression was not related to histological type, clinical stage, or retroperitoneal lymph node metastasis, but the expression level was significantly higher (P = 0.002) in patients with recurrence than those without recurrence, and progression-free survival and complete response rate to chemotherapy were also improved in patients with RECQL1-low expression (n = 39) stage III/IV EOC (P = 0.02 and P <0.05 vs RECQL1-high expression patients (n = ), respectively). A cell proliferation and colony formation assays revealed significantly less growth of RECQL1(-) cells compared to RECQL1(+) cells. A flow cytometry using annexin V -FITC and propidium iodide (PI) staining revealed a significant increase in apoptotic RECQL1(-) cells. Cell cycle analysis showed a significantly greater distribution in subG1 phase indicating apoptotic cells in RECQL1(-) cells than in RECQL1(+) cells.
  
  
  CONCLUSIONS
  These results suggest that RECQL1 is a prognostic factor for EOC and that RECQL1 contributes to potential malignancy by inhibiting apoptosis.
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. yoko-m15@cc.hirosaki-u.ac.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. yokoyama@cc.hirosaki-u.ac.jp.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki, 036-8562, Japan. hidemi_yoshida@gakushikai.jp.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. yuuki59@cc.hirosaki-u.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Osawa
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. makito@cc.hirosaki-u.ac.jp.
authors.forename: Makito
authors.initials: M
authors.lastname: Mizunuma
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. shigeryu@cc.hirosaki-u.ac.jp.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Shigeto
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. futagami@cc.hirosaki-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Futagami
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki, 036-8562, Japan. timaizumi@cc.hirosaki-u.ac.jp.
authors.forename: Tadaastu
authors.initials: T
authors.lastname: Imaizumi
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, 5-Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. mizunuma@cc.hirosaki-u.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Mizunuma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D053484:RecQ Helicases