The molecule threonyl tRNA-synthetase may provide value as a serum diagnostic marker and a potential target of therapy for ovarian cancer, according to the results of a study reported by Wellman et al in BMC Cancer. In addition, the mortality risk was slightly reduced for patients with high expression of this molecule within their tumors.
Although there has been remarkable progress in the management of gynecologic cancers, ovarian cancer remains a particularly lethal malignancy. Contributing factors that portend a poor prognosis include the inability to detect early-stage disease and the capacity of ovarian cancer cells to manipulate the tumor microenvironment. The current biomarker for accurate determination of ovarian cancer prognosis, cancer antigen 125 (CA-125), leaves much to be desired.
Since ovarian cancer is highly angiogenic, current research into future diagnostic and treatment targets has centered on the expression of angiogenic signaling molecules, including hypoxia-inducible factor-α and vascular endothelial growth factor (VEGF). Another possible angiogenic factor is threonyl tRNA-synthetase, and studies have shown that the threonyl tRNA-synthetase inhibitor borrelidin has an antiangiogenic effect. Thus, investigators from the University of Vermont explored the relationship between this molecule and ovarian cancer.
Association Between Overexpression of Molecule and Increased Survival
Levels of threonyl tRNA-synthetase were analyzed within normal and malignant tissues from 70 patient records of the Fletcher Allen Health Care/University of Vermont between 1999 and 2003. The control group consisted of 12 patients who were identified as having benign pathologies.
There was a significant positive correlation (P < .001) between increasing disease stage and threonyl tRNA-synthetase staining intensity in ovarian tumor cells. Overexpression of threonyl tRNA-synthetase was also associated with VEGF. In addition, it was found that extracellular threonyl tRNA-synthetase promoted endothelial cell migration and angiogenesis. Although this molecule was secreted by ovarian cancer cells, and patient serum threonyl tRNA-synthetase was related to tumor threonyl tRNA-synthetase and angiogenic markers, it did not achieve significance with respect to tumor stage.
As for a comparison between CA-125 and threonyl tRNA-synthetase, the levels of CA-125 in ovarian cancer patients were much lower than levels of threonyl tRNA-synthetase (0.145–12.0 pg/mL vs 266–896 pg/mL). Of note, although overall expression of CA-125 in patients with advanced-stage ovarian cancer was a marker for increased mortality, overexpression of threonyl tRNA-synthetase was associated with increased survival in patients with advanced-stage ovarian cancer.
The results of this study suggest a novel link between threonyl tRNA-synthetase expression and ovarian cancer and may confirm an association between this molecule and its angiogenic potential in the ovarian cancer microenvironment. In addition, threonyl tRNA-synthetase may provide value as a serum diagnostic marker and a potential target of therapy for ovarian cancer, according to the investigators.
Moreover, this study produced two unexpected results. First, threonyl tRNA-synthetase was overexpressed in infiltrating leukocytes. Second, the mortality risk was slightly reduced for patients with high expression of threonyl tRNA-synthetase within their tumors.
“The antigenic properties of threonyl tRNA-synthetase and the known role for immune cell signaling in angiogenesis encourage future study of threonyl tRNA-synthetase in immune cell responses to ovarian tumors,” concluded the investigators.
Karen M. Lounsbury, PhD, of the Department of Pharmacology, University of Vermont College of Medicine, Burlington, is the corresponding author of the article in BMC Cancer.
The study authors reported no potential conflicts of interest.
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