Selenium binding protein 1 (SELENBP1) was identified to be the most significantly down-regulated protein in ovarian cancer cells by a membrane proteome profiling analysis. SELENBP1 expression levels in 4 normal ovaries, 8 benign ovarian tumors, 12 borderline ovarian tumors and 141 invasive ovarian cancers were analyzed with immunohistochemical assay. SELENBP1 expression was reduced in 87% cases of invasive ovarian cancer (122/141) and was significantly reduced in borderline tumors and invasive cancers (p < 0.001). Cox multivariate analysis within the 141 invasive cancer tissues showed that SELENBP1 expression score was a potential prognostic indicator for unfavorable prognosis of ovarian cancer (hazard ratio [HR], 2.18; 95% CI 5 1.22-3.90; p 5 0.009). Selenium can disrupt the androgen pathway, which has been implicated in modulating SELENBP1 expression. We investigated the effects of selenium and androgen on normal human ovarian surface epithelial (HOSE) cells and cancer cells. Interestingly, SELENBP1 mRNA and protein levels were reduced by androgen and elevated by selenium treatment in the normal HOSE cells, whereas reversed responses were observed in the ovarian cancer cell lines. These results suggest that changes of SELENBP1 expression in malignant ovarian cancer are an indicator of aberration of selenium/androgen pathways and may reveal prognostic information of ovarian cancer. ' 2005 Wiley-Liss, Inc.Key words: ovarian cancer; membrane proteome profiling; 2-D PAGE; selenium binding protein 1; prognostic marker; androgen; methylselenocysteine Despite advances in cancer therapeutic agents in recent years, approximately 14,000 women still die of ovarian cancer each year in the United States, making it the most lethal of the gynecological malignancies. 1 Currently, surgical debulking followed by chemotherapy is the major treatment approach for ovarian cancer. Most cases of ovarian cancer are diagnosed at advanced stages when the prognosis for 5-year survival is poor. 2 Developing new diagnostic technique and improving current therapeutic strategy are the main directions to fight this morbid disease.Multiple genomic and proteomic approaches have been applied to identify disease-associated biomarkers for diagnosis and disease management. Applying cDNA and oligo microarray technology have enabled scientists to look into the global differences in gene expression between normal and cancer cells. 3 For proteomic approaches, two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by protein identification using mass spectrometry has been the primary technique for biomarker discovery. 4,5 Membrane-associated proteins have been suggested to be a potential resource for biomarker screening. 6 In our pilot study of the use of 2-D PAGE to profile membrane-associated proteins of normal ovarian surface epithelial cells and ovarian cancer cell lines, selenium binding protein 1 (SELENBP1) was identified as the most significantly down-regulated protein in the cancer cells.The human selenium binding protein gene (...
Purpose: Novel biomarkers are urgently needed to increase the sensitivity of CA125 for the early detection of ovarian cancer. Indeed, it has been shown that as much as 20% of early-stage patients do not express significant levels of this biomarker.Therefore, the possibility of using autoantibodies directed against tumor-associated antigens as putative cancer markers is being more examined. Indeed, many autoantibodies have recently been shown to correlate with cancer patient prognosis or to be suitable for detection of the disease. Experimental Design: In this study, we have used a new approach involving the use of proteomics, immunology, and ELISA methods to identify relevant autoantibodies in the plasma of ovarian cancer patients. To do so, we developed an innovative technique called two-dimensional differential gel electrophoresis analysis of immunoprecipitated tumor antigens.Results: This strategy allowed us to successfully identify novel circulating autoantibodies directed against the S100A7 protein in the plasma of ovarian cancer patients. Further real-time reverse transcription-PCR and immunohistochemical studies confirmed that the S100A7 mRNA and protein were highly expressed in ovarian tumors but absent in normal and benign tissues. Moreover, a preliminary study involving 138 patients confirmed that the plasma levels of anti-S100A7 antibodies are significantly elevated in early-and late-stage ovarian cancer patients compared with healthy controls and with patients with benign gynecologic diseases. Conclusions: This shows that our approach is a valuable tool to successfully identify autoantibodies and tumor-associated antigens in cancer patients and that future research assessing their putative clinical usefulness would be worthwhile.Ovarian cancer is the leading cause of gynecologic cancer death worldwide. In the United States, it is the eighth most common cancer among women and the fifth most common cause of cancer death, with about 20,180 new cases and 15,310 deaths expected in 2006 (1). However, the relatively asymptomatic nature of early-stage disease and the lack of adequate screening tests have resulted in the majority of cases presenting with a late-stage disease (2). Currently, clinicians rely on a combination of serum CA125 levels and imaging to diagnose ovarian cancer in suspected patients and monitor treatment response. However, due to its low sensitivity, the currently used test to quantify the CA125 serum marker is not adequate for early detection (3). Indeed, up to 20% of ovarian cancers fail to express significant levels of the maker (4). Thus, there is an urgent need for new ovarian cancer biomarkers that could improve the sensitivity of ovarian cancer early detection.The hunt for cancer biomarkers in the serum/plasma of patients with cancer is based on the observation that some lowmolecular weight proteins that reflect the pathologic state of the patients are shed into the bloodstream (5). Therefore, because our immune system constantly surveys the body for ''nonself'' antigens,...
Robotic surgery is a minimally invasive alternative to laparoscopy for the surgical treatment of endometrial cancer and cervical cancer. Its role in ovarian cancer is just starting to be explored.
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