RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative marker against ovarian cancer

PLoS One. 2013 Aug 9;8(8):e72820. doi: 10.1371/journal.pone.0072820. eCollection 2013.

Abstract

Objective: This study analyzed the clinicopathological correlation between ovarian cancer (OC) and RECQL1 DNA helicase to assess its therapeutic potential.

Methods: Surgically resected OC from 118 retrospective cases, for which paraffin blocks and all clinical data were complete, were used in this study. RECQL1 and Ki-67 immunostaining were performed on sections to correlate RECQL1 staining with subtype and patient survival. Ten OC and two normal cell lines were then examined for RECQL1 expression and were treated with siRNA against RECQL1 to assess its effect on cell proliferation.

Results: Of the 118 cases of adenocarcinoma (50, serous; 26, endometrioid; 21, clear cell; 15, mucinous; 6, other histology), 104 (90%) showed varying levels of RECQL1 expression in the nuclei of OC cells. The Cox hazards model confirmed that diffuse and strong staining of RECQL1 was correlated with histological type. However, RECQL1 expression did not correlate with overall patient survival or FIGO stage. In vitro, RECQL1 expression was exceptionally high in rapidly growing OC cell lines, as compared with normal cells. Using a time-course analysis of RECQL1-siRNA transfection, we observed a significant inhibition in cell proliferation.

Conclusions: RECQL1 DNA helicase is a marker of highly proliferative cells. RECQL1-siRNA may offer a new therapeutic strategy against various subtypes of OC, including platinum-resistant cancers, or in recurrent cancers that gain platinum resistance.

MeSH terms

  • Adenocarcinoma, Clear Cell / enzymology
  • Adenocarcinoma, Clear Cell / genetics*
  • Adenocarcinoma, Clear Cell / mortality
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Mucinous / enzymology
  • Adenocarcinoma, Mucinous / genetics*
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / pathology
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cystadenocarcinoma, Serous / enzymology
  • Cystadenocarcinoma, Serous / genetics*
  • Cystadenocarcinoma, Serous / mortality
  • Cystadenocarcinoma, Serous / pathology
  • DNA Repair*
  • Female
  • Gene Expression
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Proportional Hazards Models
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RecQ Helicases / antagonists & inhibitors
  • RecQ Helicases / genetics*
  • RecQ Helicases / metabolism
  • Retrospective Studies
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • RNA, Small Interfering
  • RecQ Helicases

Grants and funding

The authors have no support or funding to report.