Serum Glycome Profiling: A Biomarker for Diagnosis of Ovarian Cancer

During the development of cancer, changes in cellular glycosylation are observed, indicating that alterations of the glycome occur in extracellular fluids as well as in serum and could therefore serve as tumor biomarkers. In the case of epithelial ovarian cancer (EOC), common tumor markers such as CA125 are known to have poor specificity; therefore, better biomarkers are needed. The aim of this work was to identify new potential glycan biomarkers in EOC-patients. N-Glycans were cleaved from serum glycoproteins from 63 preoperative primary EOC-patients along with 33 age-matched healthy women, permethylated, and analyzed using MALDI-TOF mass spectrometry. A value named GLYCOV was calculated from the relative areas of the 11 N-glycan biomarkers revealed by SPSS statistical analyses, namely four high-mannose and seven complex-type fucosylated N-glycans. GLYCOV diagnosed primary EOC with a sensitivity of 97% and a specificity of 98.4% whereas CA-125 showed a sensitivity of 97% and a specificity of 88.9%. Our study is the first one to compare glycan values with the established tumor marker CA125 and to give better results. Therefore, the N-glycome could potentially be used as a biomarker

Parameters fit to the model in Eq 1, originally presented by Rahbar et al. [3].

<p>The parameters fit to each human vessel specimen in the first six columns with the mean and standard deviation of the human data in the seventh column and the mean and standard deviation of rat mesenteric vessels from Rahbar et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0183222#pone.0183222.ref003" target="_blank">3</a>] in the last column. Rahbar et al. tested vessel segments both upstream and downstream of a secondary lymphatic valve but found no statistical significance between the regions, so we chose to include only upstream data from their work.</p

Volumetric renderings of collagen and elastin layers within in the lymphatic vessel wall imaged using multiphoton microscopy.

<p>(A) Collagen signal as viewed from the interior of the vessel. (B) Elastin signal as viewed from the interior of the vessel. The bottom panels show composite renderings of collagen (white) and elastin (green) within the interior surface of the vessel (C) and the exterior surface (D). Volumetric renderings of multiphoton image data were performed using the software FluoRender [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0183222#pone.0183222.ref025" target="_blank">25</a>]. Scale bar 100 μm.</p

Collagen and elastin orientation as quantified by FFT.

<p>The mean collagen fibre orientation from the 6 specimens is given in blue, and the mean elastin orientation is given in red. Error bars indicate standard deviation. Orientation angles from -90° to 90°, with the axial length of the vessel orientated at 0°. Asterisks indicate a significant statistical difference between collagen and elastin orientation as detected via T-test.</p

Isolation and biomechanical testing of cannulated vessels.

<p>(A) Example of lymphatic tissue excised during cytoreductive surgery along the retroperitoneal vessels. (B) A schematic of the experiments. The vessel was cannulated to a micropipette tip connected to a pressure reservoir at one end and an axial force transducer at the other. Transmural pressure was increased by adjusting the height of the pressure reservoir, and axial stretch was applied using a calibrated micrometer. An example of an image of a cannulated vessel can be seen in the inset. (C) Photograph of the cannulation chamber. This chamber was fixed on top of a stereo light microscope for imaging and measurement of vessel diameter.</p

British Gynaecological Cancer Society (BGCS) Uterine Cancer Guidelines: Recommendations for Practice

The remit of this guideline is to collate and propose evidence-based guidelines for the diagnosis and management of uterine cancer. This document covers all uterine cancers of any histological type