Mohl Daniel A, Lagies Simon, Lonzer Alexander, Pfäffle Simon P, Groß Philipp, Benka Moritz, Jäger Markus, Huber Matthias C, Günther Stefan, Plattner Dietmar A, Juhasz-Böss Ingolf, Backhaus Clara, Kammerer Bernd
Core Competence Metabolomics, Hilde-Mangold-Haus, University of Freiburg, 79104 Freiburg, Germany.
Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany.
Cells. 2025 Apr 22;14(9):626. doi: 10.3390/cells14090626.
Ovarian carcinoma is a gynecological cancer with poor long-term survival rates when detected at advanced disease stages. Early symptoms are non-specific, and currently, there are no adequate strategies to identify this disease at an early stage when much higher survival rates can be expected. Ovarian carcinoma is a heterogeneous disease, with various histotypes originating from different cells and tissues, and is characterized by distinct somatic mutations, progression profiles, and treatment responses. Our study presents a targeted metabolomics approach, characterizing seven different ovarian (cancer-) cell lines according to their extracellular, intracellular, and RNA-derived modified nucleoside profiles. Moreover, these data were correlated with transcriptomics data to elucidate the underlying mechanisms. Modified nucleosides are excreted in higher amounts in cancer cell lines due to their altered DNA/RNA metabolism. This study shows that seven different ovarian cancer cell lines, representing different molecular subtypes, can be discriminated according to their specific nucleoside pattern. We suggest modified nucleosides as strong biomarker candidates for ovarian cancer with the potential for subtype-specific discrimination. Extracellular modified nucleosides have the highest potential in the distinguishing of cell lines between control cell lines and themselves, and represent the closest to a desirable, non-invasive biomarker, since they accumulate in blood and urine.
卵巢癌是一种妇科癌症，在疾病晚期被发现时长期生存率较低。早期症状不具有特异性，目前尚无足够的策略在可预期更高生存率的早期阶段识别这种疾病。卵巢癌是一种异质性疾病，有源自不同细胞和组织的多种组织学类型，其特征为独特的体细胞突变、进展情况和治疗反应。我们的研究提出了一种靶向代谢组学方法，根据七种不同卵巢（癌）细胞系的细胞外、细胞内和RNA衍生修饰核苷谱对其进行表征。此外，这些数据与转录组学数据相关联以阐明潜在机制。由于癌细胞系中DNA/RNA代谢改变，修饰核苷的排泄量更高。本研究表明，代表不同分子亚型的七种不同卵巢癌细胞系可根据其特定核苷模式进行区分。我们认为修饰核苷是卵巢癌强有力的生物标志物候选物，具有进行亚型特异性区分的潜力。细胞外修饰核苷在区分对照细胞系和其自身细胞系方面潜力最大，并且由于它们在血液和尿液中积累，最接近理想的非侵入性生物标志物。
