Abstract
ObjectiveThis study analyzed the clinicopathological correlation between ovarian cancer (OC) and RECQL1 DNA helicase to assess its therapeutic potential.MethodsSurgically 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.ResultsOf 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.ConclusionsRECQL1 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.
Highlights
Ovarian cancer (OC) represents about 30% of all cancers of the female reproductive system
Resected specimens revealed that 50 patients were serous adenocarcinoma, 26 were endometrioid adenocarcinoma, 21 were clear cell adenocarcinoma, 15 were mucinous adenocarcinoma, and 6 were of other histology, including 3 squamous cell carcinoma, 2 mixed carcinoma and 1 transitional cell carcinoma
The apparent growth inhibition of cancer cells is not due to the retardation of cell growth but is due to killing of viable OC cells and reduction of cell number caused by mitotic cell death. For both serous and endometrioid adenocarcinoma, combination therapy with carboplatin and paclitaxel is an effective strategy and gives rise to an excellent therapeutic result, even if the cancer is found at an advanced stage
Summary
Ovarian cancer (OC) represents about 30% of all cancers of the female reproductive system. 75% of patients with advanced (stage III) OC represent with recurrence after surgery, which is fatal [1]. This is largely ascribed to a lack of early warning symptoms and a lack of diagnostic tests that allow early detection of OC and its recurrence [2]. Two subgroups of notorious OCs, histologically subclassified as clear cell adenocarcinoma and mucinous adenocarcinoma, are known to be resistant to various anticancer drugs, including the DNAinteracting platinum derivatives. These profiles of OCs represent serious problems among gynecological oncologists
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