Biskup Karina, Stellmach Caroline, Braicu Elena Ioana, Sehouli Jalid, Blanchard Véronique
Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany.
European Competence Center for Ovarian Cancer, Department of Gynecology, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 13353 Berlin, Germany.
Diagnostics (Basel). 2021 Jun 23;11(7):1143. doi: 10.3390/diagnostics11071143.
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.
糖胺聚糖是长的多糖链，主要存在于结缔组织中。恶性细胞周围组织中糖胺聚糖的修饰表达已被证明在多种癌症中有助于肿瘤进展、侵袭性状态和转移。卵巢癌是最致命的妇科恶性肿瘤之一，由于缺乏明显症状且早期疾病标志物不可用，导致其诊断较晚。我们首次在分子水平上研究了糖胺聚糖的变化，作为原发性上皮性卵巢癌的一种新型生物标志物。为此，用软骨素酶ABC消化了一组68个样本的血清，软骨素酶ABC将硫酸软骨素释放为二糖。经过标记和纯化后，通过高效液相色谱法对其进行测量，得到了八种二糖的图谱。我们根据所测具有统计学相关性的二糖丰度，提出了一种名为“CS-生物”的基于糖胺聚糖的新型评分。将CS-生物的性能与CA125进行了比较，CA125是常规诊断中临床使用的血清肿瘤标志物。CS-生物比CA125具有更好的敏感性和特异性。它在区分早期患者和健康对照方面更合适，这对肿瘤学家来说非常重要。
