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Published on: January 12, 2020
The level of RECQL1 expression is a prognostic factor for epithelial ovarian cancer
Yoko Matsushita1, Yoshihito Yokoyama2, Hidemi Yoshida3
1Department 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.
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.
