Chondroitin Sulfate Disaccharides, a Serum Marker for Primary Serous Epithelial Ovarian Cancer

Abstract

Glycosaminoglycans are long polysaccharidic chains, which are mostly present in connective tissues. Modified GAG expression in tissues surrounding malignant cells has been shown to contribute to tumor progression, aggressive status and metastasis in many types of cancer. Ovarian cancer is one of the most lethal gynecological malignancies due to its late diagnosis because of the absence of clear symptoms and unavailability of early disease markers. We investigated for the first time GAG changes at the molecular level as a novel biomarker for primary epithelial ovarian cancer. To this end, serum of a cohort of 68 samples was digested with chondroitinase ABC, which releases chondroitin sulfate into disaccharides. After labeling and purification, they were measured by HPLC, yielding a profile of eight disaccharides. We proposed a novel GAG-based score named “CS- bio” from the measured abundance of disaccharides present that were of statistical relevance. CS-bio’s performance was compared with CA125, the clinically used serum tumor marker in routine diagnostics. CS-bio had a better sensitivity and specificity than CA125. It was more apt in differentiating early-stage patients from healthy controls, which is of high interest for oncologists.

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles

“…Leading to the question what difference in the tissue composition influences the binding and accumulation of VSOPs in the DSS-induced colitis compared to the missing accumulation in transfer colitis. To understand the distinct binding-capacity of VSOP in the different colitis models, the ECM composition was elucidated by HPLC, as described in Volpi et al (2014) and Biskup et al (2021) , and histopathology.…”

Straightforward Analysis of Sulfated Glycosaminoglycans by MALDI-TOF Mass Spectrometry from Biological Samples

“…Their complex sulfation patterns mediate very specific regulation of or binding to proteins and thus represent a molecular code [3]. These sulfation patterns can be severely altered under pathological conditions, such as inflammation and cancer, thereby affecting their function [4][5][6][7]. To better understand the structure-function relationships of sulfated GAGs and their resulting role in diseases, effective tools for the analysis of these highly complex glycans are desirable.…”

“…As GAGs are made of extremely long polymer chains, bottom-up strategies are used to characterize their disaccharide compositions. Typical workflows consist of lengthy protocols, including GAG enrichment and enzymatic depolymerization, followed by numerous intermediate purification steps [4,12,13]. The enzymatic cleavage of CS (or DS) with chondroitinase ABC into disaccharides results in the unsaturation of internal GlcA (or iduronic acid, respectively) between the fourth and the fifth carbon atoms.…”

“…The enzymatic cleavage of CS (or DS) with chondroitinase ABC into disaccharides results in the unsaturation of internal GlcA (or iduronic acid, respectively) between the fourth and the fifth carbon atoms. All the disaccharides produced and/or used in this study contain this unsaturation, notated as ∆ 4,5 . As a result, the isomericity between GlcA and iduronic acid is lost; therefore, CS and DS are analyzed together and cannot be differentiated from each other.…”

“…GAG analysis is very frequently performed via high-performance liquid chromatography, liquid chromatography coupled to electrospray ionization or ion-mobility mass spectrometry [4,[13][14][15][16]. In addition, some workflows have been developed to analyze GAG from tissue biopsies [17,18].…”